14: Drugs Used in Malignant Diseases and For Immunosuppression

14.
MALIGNANT DISEASES AND IMMUNOSUPPRESSION
Chapter 14
MALIGNANT DISEASES AND

IMMUNOSUPPRESSION
14: DRUGS USED IN MALIGNANT DISEASES AND FOR IMMUNOSUPPRESSION
Though current treatment is given with curative or palliative intention, the main
approaches with dealing malignancies are surgical intervention, radiation and
chemotherapy. Treating cancer with cytotoxic drugs is the main method of treatment
for only a few malignant disease; but it’s increasingly use as an adjunct to surgery or
irradiation in a range of common types of malignancy.
In this chapter, drug treatment in malignant diseases and for immunosuppression is
discussed under the following headings:
14.1. Cytotoxic drugs p.503

14.1.1 Alkylating drugs p.509
14.1.2 Cytotoxic antibiotics p. 511
14.1.3 Antimetabolites p. 514
14.1.4 Vinca alkaloids and etoposide p. 518
14.1.5 Other antineoplastic drugs p. 520
14.2 Drugs affecting the immune response p. 529
14.2.1 Antiproliferative immunosuppressants p.529
14.2.2 Corticosteroids and other immunosuppressants p.531
14.2.3 Rituximab p. 532
14.2.4 Interferons p.534
14.2.5 Aldesleukin p. 534
14.2.6 BCG immunotherapeutics p.534
14.3 Sex hormones and hormone antagonists in malignant diseases p. 534
14.3.1 Estrogens p. 534
14.3.2 Progestogens p. 535
14.3.3 Androgens p. 535
14.3.4 Hormone antagonists p.536
14.3.4.1 Breast cancer p.536
14.3.4.2 Prostate cancer and gonadorelin analogue p. 537
14.3.4.3 Somatostatin analogues p. 538
14.1 CYTOTOXIC DRUGS advice from the specialist oncologist.

Along with its anti-cancer activity
14.1.1 ALKYLATING DRUGS cytotoxic drugs have also the potential
14.1.2 CYTOTOXIC ANTIBIOTICS for damage to normal tissue. This
14.1.3 ANTIMETABOLITES property determined that drugs could be
14.1.4 VINCA ALKALOIDS AND given intermittently and that time had to
ETOPOSIDE be allowed for normal tissues to recover
14.1.5OTHER ANTINEOPLASTIC between each administration of cytotoxic
DRUGS drugs. The tumors also rapidly
developed resistance to single agents
and this is why the intermittent
Like the disease, the treatment of cancer
combination chemotherapy principle was
is also a complex one. It is better to take
503
14. MALIGNANT DISEASES AND IMMUNOSUPPRESSION
established. Several drugs were threatening complications from

combined together, chosen on the basis myelosuppression. Modern cytotoxic
of differing mechanisms of actions and chemotherapy has improved out of all
non-overlapping toxicities. In an recognition from those early days and
increasing number of cases newer cytotoxic drugs, often analogues
chemotherapy may be combined with of original drugs, are frequently
radiotherapy or surgery or both as either associated with significantly fewer side
neoadjuvant (Pre-surgery chemotherapy effects.
for early and locally advanced cancer) Most currently used anticancer drugs
treatment or as adjuvant (Chemotherapy have their main effects on cell division;
following local treatment for early because of this effect they will affect all
cancer) treatment. Drug combination are rapidly dividing normal tissues and thus
frequently more toxic than single drug they are likely to produce, to a greater or
but may have the advantage in certain lesser extent of the following toxic effects
tumors of enhanced response, reduced are :
development of drug resistance and
increased survival. However, for some Bone marrow toxicity with decreased
tumors, single-agent chemotherapy leucocyte production and thus
remains the treatment of choice. decreased resistance to infection,
Cytotoxic drugs may be given with a impaired wound healing, depression
curative intent or to palliate the of growth in children, sterility,
symptoms or it may aim to prolong the teratogenecity, loss of hair, and
survival. damage to gastrointestinal
epithelium.
Cytotoxic drugs are categorized into
different classes according to They can also in certain circumstances,
characteristic anti-tumor activity, sites of be carcinogenic. A number of cytotoxic
action and toxicity. drugs will cause severe local tissue
necrosis if leakage into the extravascular
compartment occurs. In addition, if there
SIDE EFFECTS OF CYTOTOXIC
is rapid cell destruction with extensive
DRUGS
purine catabolism, urates may
precipitate in the renal tubules and
The side effects of anti-cancer drugs are cause kidney damage. All cytotoxic
legendary and have created fear in both drugs produce severe nausea and
the medical profession and the general vomiting. Some compounds have
public. The situation has improved from particular toxic effects which are specific
the early days of cytotoxic chemotherapy for them. These will be discussed under
where persistent and prolonged nausea the individual drugs.
and vomiting were the rule and life
WARNINGS
Cytotoxic drugs should be administered under the supervision of a physician with
sufficient experience in cancer chemotherapy at medical institutions in which
appropriate medical treatment can be made in emergency to the patients.
REGARDING DOSAGE REGIMENS

Although dose statements have been given in this chapter, still product literature
needs to be consulted.
Despite the advances, chemotherapy anticancer drugs such as bone marrow

still carries many potentially serious side suppression, emesis, extravasation,
effects and should be used only by hyperuricaemia are described below with
practitioners with considerable skills and the measures to control them.
experiences. The main side effects with
504
Nausea and vomiting: is the most Extravasation: or leakage of cytotoxic

common terrified effect of cancer drugs into the extravascular
treatment. The incidence and severity of compartments leads several local tissue
nausea and vomiting varies depending necrosis. To reduce the risk of
on the type, dose, schedule, combination extravasation injury it is recommended
of medication of chemotherapy and the that they should be given by
patient’s characteristics. Symptoms may appropriately trained hands. Attention
be acute (occurring with in 24 hours of should be paid to the manufactures’
treatment), delayed (occurring after 24 recommendations for administration.
hours of initiating treatment) and Patients should be asked to report any
anticipatory (occurring prior to pain or burning at the site of injection
subsequent doses). Delayed and immediately.
anticipatory symptoms are more difficult Hyperuricaemia: which can result in
to control than acute one and require uric acid crystals formation in the urinary
different managements. tract with associated renal dysfunction is
Severe vomiting can be produced by the a major complication of treatment of non-
platinum based drugs such as Hodgkin’s lymphoma, leukaemia and
dacarbazine, high doses of myelo-proliferative diseases. Patients
cyclophosphamide, cisplatin and taxene. should be adequately hydrated.
Moderately emetogenics are Increased urinary volume decreases the
doxorubicine, intermediate and low dose concentration of urate in urine and thus
of cyclophoshamide, mitoxantrone and minimizes the problem. Alkalinisation of
high dose of methotrexate (0.1 – 1.2 urine should be initiated to maintain
g/m2). The less severe or mild emesis is urine pH at least 7. Other than this,
found with fluorouracil, etoposide, Allopurinol should be started 24 hours
methotraxate (less than 100 mg/m2), the before treating such tumors, and should
vinca alkaloids and abdominal be continued for 7-10 days; The dose of
radiotherapies. Mercaptopurine or Azathioprine should
To prevent emesis a specific (5HT3) be reduced if Allopurinol needs to be
serotonin antagonist, granisetron is given concomitantly.
used. The 5HT3 antagonists are highly Bone Marrow Suppression: is caused
effective in controlling early emesis and by all the cytotoxic drugs except
have largely replaced the use of high- vincristine and bleomycine. It commonly
dose of intravenous metoclopramide. occurs 7-10 days after administration,
Granisetron can more readily be given but also delayed in certain drugs, such
as a single intravenous dose for patients as carmastine, lomustine, and
receiving cisplatin and non-cisplatin melphalan. To overcome these problem
based regimes. In addition it is approved peripheral blood counts must be
for oral use for cisplatin-based (highly checked before each treatment, and
emetogenic) antineoplastic therapy doses should be reduced or therapy
unlike ondansetron. The 5HT3 receptor delayed if bone marrow has not
antagonists [Granisetron] currently recovered.
marketed have proved to be less Fever in a neutropenic patient should
effective in controlling delayed nausea receive parental broad-spectrum
and vomiting than they are at controlling antibiotics. Appropriate culture and
acute emesis. Further there is no good sensitivity tests should be done as soon
scientific rationale for the use of 5HT3 as possible.
antagonists in treating delayed nausea
and vomiting since serotonin has not Colony stimulating factors, G-CSF are
been shown to be released during the sometimes successful in selected
delayed phase. The addition of patients depending on the duration and
lorazepam to antiemetic therapy is severity of the neutropenia.
sometimes helpful to prevent anticipatory Alopecia: many but not all the cytotoxic
symptoms. drugs are capable of causing hair loss.
505
Scalp cooling can sometimes be used to dose of levofolinic acid is half of folinic
reduce hair loss with doxorubicine, but in acid.
general this side effect can be prevented
only by selection of cytotoxic drugs
CALCIUM FOLINATE
where this is possible. Hair always
regrows on completion of chemotherapy. (Calcium leucovorin)
No pharmacological methods of
preventing reversible hair loss are Indications: methotrexate induced
available. mucositis and myelosuppression
Pregnancy: most cytotoxic drugs are Cautions: avoid simultaneous
teratogenic and should not be administration of methotrexate, not
administered during pregnancy, indicated for pernicious anemia or other
especially during first trimester. megaloblastioc anemia due to vitamin
B12 deficiency; pregnancy and breast-
Cardio-toxicity: this is a rare side effect feeding
of chemotherapy, usually associated
with doxorubicine. It is dose related and Interactions: antiepileptics; plasma
can largely be prevented by keeping the concentration of phenobarbital,
total dose with in the safe range. phenytoin and primidone possibly
reduced (see also Appendix-2)
Neuro-toxicity: this occurs
predominantly with the plant alkaloids Contraindication: intrathecal injection.
and platinum analogues. It is dose Side-effects: rarely pyrexia after
related and chemo therapy usually parental use
stopped before the development of the Dose: expressed in terms of folinic acid
significant polyneuropathy. This is only
partially reversible. As an antidote to methotrexate (usually
started 24 hours after the beginning of
Sterility: some anticancer drugs, methotrexate infusion), usually up to 120
specially alkylating agents, may cause mg in divided doses over 12-24 hours by
sterility. This can be irreversible. In male intramuscular or intravenous injection or
storage of sperm is the only important intravenous infusion, followed by 12-15
consideration when chemotherapy is mg intramuscularly or 15 mg by mouth
given with curative intentions. every 6 hours for the next 48 –72 hours.
Suspected methotrexate overdose,
Drugs to prevent cytotoxic-induced
immediate administration of folinic acid
side-effects
at a rate not exceeding 160 mg/minute in
a dose equal to (or higher than) the dose
Methotrexate-induced mucosities and of methotrexate
myelosuppression
Proprietary Preparations
Folinic acid (calcium folinate) is used to Biofol (Incepta), Tab. 15 mg, Tk. 25.00/Tab.
counteract the folate-antagonist action of Folinex (Beacon), Inj. 50mg/ml, Tk.500.00/Vial
methotrexate and thus speed recovery
from methotrexate-induced mucositis CALCIUM LEVOFOLINATE
and myelosuppression. (Calcium levoleucovorine)
When folinic acid and fluorouracil are
used together in metastatic colorectal Indications: same as that of calcium
cancer the response-rate improves folinate
compared to that with fluorouracil alone Cautions: same as that of calcium
(see also section 15.1.2.1). calcium folinate
Levofolinic acid: The calcium salt of Side-effects: same as calcium folinate
levofolinic acid is the single isomer of
folinic acid. It is used as folinic acid. The Dose: express in terms of levofolinic
acid
506
As an antidote to methotrexate (usually FILGRASTIM

started 24 hours after the beginning of
methotrexate injection), usually 7.5 mg, (Recombinant human granulocyte colony
by intramuscular injection or by stimulating factor, G-CSF) (see also
intravenous injection or by intravenous section 15.1.4)
infusion every 6 hours for 10 doses
Indications: (specialist use only)
Suspected methotrexate overdose, reduction duration of neutropenia and
immediate administration of levofolinic incidence of febrile neutropenia in
acid at a rate not exceeding 160 cytotoxic chemotherapy for malignancy
mg/minute in a dose which is a least (except chronic myeloid leukemia and
50% of the dose of methotrexate myelodysplstic syndromes); reduction in
duration of neutropenia (and associated
Proprietary Preparation sequel) in myeloablative therapy
Leucovorine(I) (Mayne),Inj. 50mg/ml
followed by bone marrow transplan-
Tk.377.09/vial, Tk.15mg/2ml, Tk.228.78/vial
tation; mobilization of peripheral blood
progenitor cells for harvesting and
PLATINUM-INDUCED NEUTROPENIC subsequent autologous infusion; severe
INFECTION AND NEPHROTOXICITY congenital neutropenia, cyclic neutrop-
enia, or idiopathic neutropenia and
Granulocyte colony stimulating factor history of severe or recurrent infections
and granulocyte macrophage-colony (distinguish carefully from other haema-
stimulating factor are used for the tological disorders, consult product
reduction of risk of infection associated literature); persistent neutropenia in
with neutropenia. advanced HIV infection
Recombinant human granulocyte-colony Cautions: reduced myeloid precursors;
stimulating factor (rhG-CSF) stimulates monitor leucocyte count (discontinue
the production of neutrophils and may treatment if leucocytosis, consult product
reduce the duration of chemotherapy literature); monitor platelet count and
induced neutropenia and thereby reduce haemoglobin; regular morphological and
the incidence of associated sepsis; there cytogenetic bone marrow examinations
is yet no evidence that it improves recomended in severe congenital
overall survival. Filgrastim neutropenia (possible risk of
(unglycosylated rhG-CSF) and myelodysplastic syndromes or
lenograstim (glycosylated rhG-CSF) leukaemia); monitor the spleen size,
have similar effects; both have been osteoporotic bone disease (monitor bone
used in a variety of clinical settings but density if given for more than 6 months);
they do not have any clear-cut routine does not prevent other toxic effects of
indications. Prolonged use may be high dose chemotherapy; pregnancy,
associated with increased risk of breast feeding
malignancy. Molgramostim (Recom-
binant human granulocyte macrophage Interactions: possible exacerbation of
colony stimulating factor) stimulates the neutropenia with fluorouracil
production of all granulocytes and Note: use not recommended in period
monocytes. It has more side-effects than from 24 hours before to 24 hours after
granulocytes colony stimulating factor chemotherapy - for further details consult
and is ineffective in congenital product literature.
neutropenia. Contraindications: severe congenital
neutropenia with abnormal cytogenetics
Side-effects: musculoskeletal pain,
transient hypotension, disturbances in
liver enzymes and serum uric acid;
thrombocytopenia; urinary abnormalities
including dysuria; allergic reactions
507
(more common after intravenous chemotherapy. For further details

infusion), proteinuria, haematuria, and consult product literature
transient decrease in blood glucose Dose: cytotoxic induced neutropenia, by
reported; cutaneous vasculitis also subcutaneous injection, ADULT 19.2
reported, also spleenic enlargement, million units/sq.m. daily started the day
hepatomegaly, headache, diarrhoea, after completion of chemotherapy,
anaemia, epistaxis, alopecia, continued until neutrophil count is stable
osteoporosis and rash, reactions at in acceptable range (max. 28 days)
injection site; rarely reported,
exacerbation of rheumatoid arthritis, Proprietary Preparation
adult respiratory distress syndrome Granocyte(I) (Sanofi Winthrop), Inj. 34 MIU/
Dose: cytotoxic-induced neutropenia, vial, Tk. 5961.54/Vial
preferably by subcutaneous injection or
by intravenous infusion (over 30 Amifostine is used recently for the
minutes), ADULT and CHILD, 50,00,000 reduction of risk of infection related to
units/kg daily started not less than 24 neutropenia in patients undergoing
hours after cytotoxic chemotherapy, treatment with cisplatin and
continued until neutrophil count in cyclophosphamide and for the reduction
normal range, usually for up to 14 days of nephrotoxicity due to cisplatin. It is
(up to 38 days in acute myeloid also used recently to protect against
leukaemia) xerostomia during radiotherapy for head
and neck cancer.
Filastin (Incepta), Inj.,(P.F syringe) 300 UROTHELIAL TOXICITY
mcg/0.5 ml, Tk. 2,890.00/Syringe
Filgrast (Beacon), Inj., (P.F syringe) 300
Haemorrhagic cystitis is a common
mcg/0.5 ml, Tk. 2,750.00/ Syringe
Grastim (Square), Inj.,(P.F syringe) 300 manifestation of urithelial toxicity which
mcg/0.5 ml, Tk. 3,950.00/Syringe occurs with the oxazaphosphorines,
Neufil (Healthcare), Inj.,(P.F syringe) 300 cyclophosphamide and ifosfamide; it is
mcg/0.5 ml, Tk.3,920.00/ Syringe caused by the metabolite acrolin. Mesna
Neupogen (I) (Roche), Inj., 30 MIU, Tk. reacts specifically with this metabolite in
8,000.00/Vial the urinary tract, preventing toxicity.
Zarzio(I) (Sandoz), Inj.,(P.F syringe) 30
Mesna is used routinely (preferably by
MIU/0.5 ml, Tk. 21,000.00/0.5 ml Syringe
mouth) in patients receiving ifosfamide,
cyclophosphamide by intravenous route
LENOGRASTIM at a high dose (more than 2 g) or in
(Recombinant human granulocytecolony those who experienced urothelial toxicity
stimulating factor, rhG-CSF)
when given cyclophosphamide
previously.
Indications: (specialist use only)
reduction in the duration of neutropenia
and associated complications following MESNA
bone marrow transplantation for
nonmyeloid malignancy or following Indications: see notes above.
treatment with cytotoxic chemotherapy Contraindications: hypersensitivity to
associated with significant incidence of thiol containing compounds
febrile neutropenia; mobilisation of
Side-effects: nausea, vomiting, colic,
peripheral blood progenitor cells for
diarrhea, fatigue, headache, limb and
harvesting and subsequent infusion
joint pains, depression, irritability, rash,
Cautions: see under filgrastim; hypotension and tachycardia
premalignant myeloid conditions
Dose: calculated according to
Interactions: use not recommended oxalophosphorine (cyclophosphamide or
from 24 hours before until 24 hours after ifosfamide) treatment. When given by
mouth, dose is given 2 hours before
508
oxalophosphorine treatment and haemorrhagic cystitis. Cyclophospha-

repeated 2 and 6 hours after treatment; mide is a prodrug that is activated to give
when given by intravenous injection, aldophosphamide, which is then
dose is given with oxalophosphorine converted to phosphoramide mustard,
treatment and repeated 4 and 8 hours the cytotoxic molecule and acrolin which
after treatment causes haemorrhagic cystitis that can be
ameliorated by Mesna and by increasing
Proprietary Preparations fluid intake.
Ifomes (Beacon), In.j, 400 mg/Vial, Tk.
Busulfan (busalphan) has a selective
190.00/Vial
Mesna (Techno), Inj., 400 mg/Vial , Tk. effect on bone marrow, depressing the
240.00/Vial formation of granulocytes and platelets
Uromitexan (I) (Baxter), Inj. 400 mg/4 ml, Tk. in low dosage and red cells in higher
4474.50/4 ml Vial dosage. It has little or no effect on
lymphoid tissue or the gastrointestinal
14.1.1 ALKYLATING DRUGS tract. It is accordingly used in chronic
granulocytic leukaemia, in which it may
The anti-tumor alkylating agents are the increase the life expectancy by about a
oldest class of anti-cancer drugs. These year. It has a hazardous toxic effect,
molecule represents the first examples thrombocytopenia. Hyperpigmentation of
of the application of scientific rigor to the skin is a common side-effect and rarely
clinical development of drugs for the progressive pulmonary fibrosis may
treatment of cancer and the first example occur. Frequent blood count is essential
where a knowledge of the properties of to monitor bone marrow aplasia.
the cancer cells was applied to rational Busulfan is to be given with
drug design. The anti-tumor alkylating cyclophosphamide in a preparatory
agents are the most widely used anti- regimen for bone marrow transplant in
cancer drugs, being major components the treatment of refractory leukemias,
of the combination chemotherapy lymphomas and several paediatric solid
regimens for the disseminated solid tumors.
tumors and for high dose/stem cell Carmustine is given intravenously. It
support treatment regimens. The agents has similiar activity and toxicity to
having alkyl group can form covalent lomustine. This drug is used for
bonds with the cellular DNA, resulting myeloma, lymphoma, brain tumors.
inhibition or inaccurate cell replication Cumulative renal damage and delayed
with resultant mutation and cell death. pulmunary fibrosis may occur.
Cyclophosphamide is a broadly active Chlormethine (mustine) is now much
anti-cancer drug. It has pronounced less commonly used. It is a very toxic
effect on lymphocytes and is used as an drug which causes severe vomiting. The
immunosuppressant. It is used in freshly prepared injection must be given
combination chemotherapy regimens for into a fast-running intravenous infusion.
non-Hodgkin’s lymphoma, leukaemia, Local extravasation causes severe
Hodgkin’s disease, Burkit’s lymphoma, tissue necrosis.
breast cancer, ovarian carcinoma,
endometrial carcinoma, small cell lung Chlorambucil, the phenylebutyric acid
carcinoma, multiple myeloma, sarcomas. derivative of nitrogen mustard, was
Cyclophosphamide is also a useful agent synthesized, like Melphalan in an
in high dose regimen for lymphoma and attempt to produce a nitrogen mustard
solid tumors. It is usually given orally or with greater efficacy than
by intravenous injection but may also be mechlorethamine. Chlorambucil is
given intramuscularly or into the pleural relatively stable in aqueous solution and
or peritoneal cavities. Important toxic is well absorbed in oral administrations.
effects are nausea, vomiting, This is commonly used in chronic
myelosuppression, sterility, risk of acute lymphocytic leukaemia, Hodgkin’s and
non-lymphocytic leukaemia and non-Hodgkin’s lymphoma, choriocarci-
509
noma, ovarian carcinoma, breast cancer. cancer. Skin pigmentation is the

Chlorambucil is administered either as a common side-effect and allergic
single agent or combination with alveolitis, pulmonary fibrosis and
prednisone. Side-effects apart from haemorrhagic cystitis occur rarely.
marrow suppression are uncommon. Thiotepa is used as an intracavitary
However, occasionally patients develop drug for the treatment of malignant
severe widespread rashes that can effusions or bladder cancer. It is also
progress to toxic epidermal necrolysis. If occasionally used to treat breast cancer,
rash occurs further chlorambucil is but require parental administration.
contraindicated and cyclophosphamide
is substituted.
BUSULFAN
Estramustine is a combination of (Busulphan)
mustine with an estrogen used
predominantly in prostate cancer. It is Indication: chronic myeloid leukemia.
given by mouth and has both antimitotic
effect and hormonal effect. Caution: see section 14.1
Ifosfamide originated from the same Side-effects : see section 14.1and
chemical synthesis program that had notes above
produced cyclophosphamide. Ifosfamide Dose : ADULT: induction of remission,
is a pro-drug like cyclophosphamide, and 60 micrograms/kg to max 4 mg/m2 daily
is highly active in soft tissue sarcoma until the leucocyte count is 50% of the
and produced significant response rate original level; maintenance, 0.5-2 mg/m2
in non-small cell lung cancer. Ifosfamide daily. CHILD: not recommended
is administered intravenously. Although it
causes less myelosupression than Generic Preparation
cyclophosphamide, it produces dose- Tablet. 2 mg.
limiting cystitis. Mesna given prior to,
during, and after ifosfamide or CHLORAMBUCIL[ED]
simultaneously with ifosfamide prevents
haemorrhagic cystitis. Indications: chronic lymphocytic
Lomustine may act on non-dividing cells leukemia, low grade non-Hodgkin’s
and can cross blood brain barrier (BBB); lymphoma; ovarian carcinoma.
it is mainly used in the treatment of Caution: see section 14.1 and avoid in
primary and metastatic brain tumor, and porphyria
advanced Hodgkin’s disease. This
Side-effects: see section 14.1and notes
cytotoxic agent causes delayed,
above
cumulative myelotoxicity and the drug is
therefore given at intervals of 4 to 6 Dose: used alone, usually 100-200
weeks. Permanent bone marrow micrograms/kg daily for 4-8 weeks
damage may occur with prolonged use.
Nausea and vomiting are common and Proprietary Preparation
moderately severe. Leukeran (I) (GSK), Tab. 2 mg
Melphalan is used in the treatment of

CYCLOPHOSPHAMIDE [ED]
myeloma, occasionally solid tumor and
lymphomas. It is given by mouth.
Because bone marrow toxicity is delayed Indications: breast, lung, ovary, testis
the drug is usually given at intervals of 4- and bladder carcinomas. Bone and soft
6 weeks. tissue sarcomas
Hodgkin’s and Non-Hodgkin’s
Mitobronital is sometimes used to treat lymphomas. acute and chronic
chronic myeloid leukemia. lymphocytic leukaemias, neuroblastoma
Treosulfan is given by mouth or and Wilm’s tumor of childhood, multiple
intravenously and used to treat ovarian myeloma.
510
Cautions: hepatic and renal impairment Indications: see note above.

Interactions: anticoagulants, pentostatin Cautions: see section 14.1 and notes
(avoid concomitant use), muscle above
relaxants (enhance the effect of Side-effects: see section 14.1and notes
suxamethonium) (see also Appendix-2) above
Side-effects: see section 14.1 Dose: used alone, 120-130 mg/m2 PO
Dose: high dose therapy: 20- once every 6-8 weeks
40mg/kg as a single I.V. dose given at
10-20 days intervals. Medium dose Generic Preparation
therapy: 10-15 mg/kg as a single I.V. Capsule 10mg
dose weekly. Low dose therapy: 2-6
mg/kg as a single I.V. dose or in divided MELPHALAN
oral dose for 7 days & maintenance 100-
200 mg daily. CHILD not recommended Indications: mainly multiple melanoma,
breast and ovarian cancers
Proprietary Preparations Cautions: see the side-effects of
Cyclomide (Techno ), Inj, 1 gm Vial,
cytotoxic drugs and renal impairment
Tk.1,200.00/Vial
Cyclotox (Beacon), Inj., 1 gm Vial,Tk.650/Vial; Interactions: nalidixic acid (increased
Inj., 200mg Vial, Tk.180.00/Vial toxicity), cyclosporin (renal impairment);
Endoxan(I) (Baxter), Inj., 200mg, Tk.
3114.2/Vial; 500mg, Tk. 20.52/Vial; 1gm, Tk. see also Appendix-2
1374.56/Vial; Tab., 50mg, Tk. 1718/Tab. Side-effects: see the side-effects of
G-Cyclophosphamide (Gonoshasthaya), cytotoxic drugs and notes above
Tab., 50 mg, Tk. 6/Tab.
Dose: by mouth 150 micrograms/kg
daily in divided doses for 4 days
IFOSFAMIDE
repeated at an interval of 6 weeks
Indications: tumors of testes, pancreas, Proprietary Preparation
ear; nose & throat, ovary, bone, breast, Alkeran (GSK),Tab.,2mg
lungs, G I Tract, kidneys; lymphomas
and soft tissue sarcomas 14.1.2 CYTOTOXIC ANTIBIOTICS
Cautions: see section 14.1; reduce the
dose in hepatic and renal impairment Drugs in this group are used widely.
Interactions: see Appendix-2 Anthracyclines are mainly termed as
Side-effects: see the side-effects of cytotoxic antibiotics. The first
cytotoxic drugs anthracyclines in clinical use,
doxorubicin and daunorubicin, were
Dose: 8-10 g/m2 IV fractionated equally produced by Streptomyeces species.
to single daily dose for 5 consecutive The second generation idarubicin,
days or a 24 hours infusion of 5-6 g/m 2; epirubicin are synthetic anthracyclines.
use in combination with Mesna (60% of Mitoxantrone (mitozantrone) is an
total dose of Ifosfamide) anthracycline derivative.
Anthracyclines, DNA intercalators
Proprietary Preparations represent the most important class of
Holoxan(I) (Baxter), Inj., 1g, Tk. 3049.8/1 gm
anticancer drugs.
Vial; 2g, Tk. 4810.58/2 gm Vial
Ifamide(Techno), Inj., 1 gm/vial, Tk. Doxorubicin is one of the most
2,400.00/Vial ; 2 gm/vial, Tk. 4,500.00/Vial successful and widely used anti-tumor
Xifos (Beacon), Inj., 1 gm/vial, Tk. drugs. It is used to treat the acute
1,800.00/Vial; 2 gm/vial, Tk. 3,200.00/Vial leukaemia’s, lymphomas and a variety of
solid tumors. It acts by DNA strand
LOMUSTINE breakage mediated by anthracycline
effects on topoisomerase II, the activity
511
of which is markedly increased in intramuscularly to treat the lymphoma’s,

proliferating cells. It is given by fast and germ cell tumors of testis and ovary
running infusions, commonly at 21 days and also some other solid tumors. With
intervals. After infusion it is rapidly taken it’s little bone marrow suppression it
up by most tissues, but does not cross causes dermatological toxicities and
the Blood Brain Barrier (BBB). increased pigmentation. Most serious
Extravasation at the infusion site can toxic effect is pulmonary fibrosis. Basal
cause local necrosis. It is also been lung crepitations or suspicious chest X-
given in bladder instillation. Evidence is ray changes are indications to stop
available to suggest that weekly low therapy with this drug. Allergic reactions
dose administration may be associated can occur. Many develop hyperpyrexia a
with less cardiac damage. It is excreted few hours after drug administration and
mainly in the bile. In addition to the side may be prevented by simultaneous
effects common to other cytotoxic administration of corticosteroid.
agents, doxorubicin can cause Dactinomycin is one of a series of
cumulative dose related cardiac antibiotics obtained from Streptomyces
damage, leading to arrhythmias and microorganisms, principally used in
heart failure. Patients with pre existing paediatric cancer. It prevents
cardiac disease, the elderly, and those transcription and has a similar action to
who have received myocardial irradiation the anthracyclines on topoisomerase II.
should be treated cautiously. Marked It has effects on cells in all phases of the
alopecia frequently occurs. cell cycle, but it is particularly potent on
Epirubicin is structurally related to rapidly proliferating cells. It has all the
doxorubicin and clinical trials suggest cytotoxic effects described under side
that it is as effective in the treatemnt of effects of cytotoxic drugs. It is usually
breast cancer. A maximum cumulative given by IV injection and rapidly
dose of 0.9-1 g/m2 is recommended to disappears from the plasma and does
help to avoid cardiotoxocity. Like not cross the BBB.
doxorubicin it is given intravenously and Mitomycin is given intravenously to treat
bladder instillation. upper gastro intestinal and breast
Aclarubicin and idarubicin are cancers and by bladder instillation for
anthracyclines with general properties superficial bladder tumors. It causes
similar to those of doxorubicin. They are delayed bone marrow toxicity and
both given intravenously. Idarubicin may therefore it is usually administered at 6
also be given by mouth. weeks intervals. Prolonged use may
Daunorubicin also has general result in permanent bone marrow
properties similar to those of damage. It may also cause lung fibrosis
doxorubicin. It should be given by and renal damage.
intravenous infusion and is indicated for
acute leukaemias. BLEOMYCIN [ED]
Mitoxantrone (mitozantrone) is
structurally related to doxorubicin. It’s Indications: squamous cell carcinoma,
main use is in breast cancer though it is lymphomas, germ cell tumors of testis
also licensed to use in non Hodgkin’s and ovary and certain solid tumors
lymphoma and adult non lymphocytic Cautions: see section 14.1; renal
leukaemia. It is given intravenously and impairment; irritant to tissue
well tolerated but myelosuppression and Side-effects: see section 14.1 and see
dose related cardiotoxicity occurs. notes above
Bleomycin is a group of metalchelating Dose: over 80 years, 15 mg/week, total
glycopeptide antibiotics that degrade 100mg; 70-79 years, 30 mg/week, total
preformed DNA, causing chain 150-200 mg; 60-69 years, 30-60
fragmentation and release of free bases. mg/week, total 200-300 mg; under 60
It is given intravenously or
512
years, 30-60 mg/week, total 500 mg; all DOXORUBICIN HCL [ED]
are given I.V. or in infusion
Indications: lymphoma, leukemia,
Proprietary Preparation breast cancer, ovarian cancer, sarcomas
Bleocin (I)(Nippon), Inj. 15000unit/vial Tk.
and varieties of solid tumors
2063.99/vial
Cautions: hepatic and renal impairment
DACTINOMYCIN caution in handling - irritant to tissue
(Actinomycin D) (see section 14.1)
Interactions: see Appendix-2.
Indications: gestational trophoblastic Side-effects: see section 14.1and see
neoplasms, Wilm’s tumor, notes above
rhabdomyosarcoma and Ewing’s
Dose: 60-75 mg/m2 I.V. every 3 weeks.
sarcoma of childhood
30 mg/m2 I.V. one days 1 and 8 every 4
Cautions: see section 14.1; caution in weeks (in combination). 15-20 mg/m2
handling- irritant to tissue instilled into bladder weekly for 4 weeks
Side-effects: see section 14.1 and see
notes above Proprietary Preparations
Doxorubicin HEXAL(I) (Hexel), Inj., 10 mg/5
Dose: CHILD: 0.40-0.45 mg/m2 (up to ml, Tk. 307.00/5 ml Vial; 100 mg/50 ml, Tk.
maximum of 0.5 mg) IV daily for 5 days 1,725.00/50 ml Vial; 200 mg/100 ml, Tk.
every 3-5 weeks. 3,080.00/100 ml Vial; 50 mg/25 ml, Tk.
ADULT: 0.40-0.45 mg/m2 IV on days. 1-5 1,096.00/25 ml Vial
Doxorub (Techno ), Inj., 10 mg/Vial, Tk.
every 2-3 weeks. 0.5 mg IV daily for 5 406.00/10 ml vial ; 50 mg/Vial, Tk. 1,590.00/50
days every 3-5 weeks. ml vial
Sindroxocin(I) (Actavis), Inj., 50mg/vial, Tk.
Generic Preparation 1560.00/vial; Inj., 10 mg/Vial, Tk.670.00/vial
Injection. 100 microgram/vial. Xorubion (Beacon), Inj., 10 mg/Vial, Tk.
300.00/10 ml/vial; 50 mg/Vial, Tk. 1,000.00/50
ml Vial
DAUNORUBICIN HYDROCHLORIDE
EPIRUBICIN HYDROCHLORIDE
Indications : see notes above.
Cautions: hepatic and renal impairment; Indications: see notes above
caution in handling-irritant to tissue (see
Cautions: hepatic impairment; caution in
section 14.1)
handling - irritant to tissue (see section
Side-effects : see section 14.1 and see 14.1)
notes above
Side-effects: see section 14.1 and
Dose : 30 to 45 mg/m2 IV for 3 days; notes above
using extravasation precautions; to be
Dose: 70 to 90 mg/m2 as a bolus
injected into a recently established
injection repeated every 3 to 4 weeks;
patent IV site through side arm of a
bolus injection over 2 to 5 minutes or as
running IV over 2 to 5 minutes; courses
a continuous infusion through a central
may be repeated after 3 to 6 weeks.
venous catheter
Proprietary Preparation
Rubicin (Beacon), Inj., 20mg/vial, Tk. 600/Vial
Erubin (Beacon), Inj., 10 mg/ 5 ml , Tk.
915.00/5 ml ; 50 mg/25 ml, Tk. 3,700.00/25 ml
Episindan(I) (Sindan), Inj. 2 mg/ml, Tk.
3,866.00/25 ml;Tk.971.00/5ml vial
Pharmorubicin(I) (Pharmacia), Inj. 50 mg/Vial,
Tk. 3704.60/Vial
513
MITOMYCIN because it tends to accumulate at these

sites, and its subsequent return to the
Indications: see notes above circulation will be associated with
myelosuppression. Systemic toxicity may
Cautions: hepatic impairment; caution in occur following intrathaecal
handling - irritant to tissue; (see section administration and blood counts should
14.1) be monitored carefully. High dose
Side-effects: see section 14.1and notes regimes (doses 10 times greater than
above the standard doses) must be followed by
Dose: 20 mg/m2 I.V. on day every 4-6 “rescue” with folinic acid.
weeks. 2 mg/m2 I.V. on days 1-5 and 8- Cytosine Arabinoside (cytarabin)
12 every 4-6 weeks. 30-40 mg instilled inhibit the synthesis of pyrimidine. It is
into bladder weekly for 4-8 weeks then given subcutaneously, intravenously or
monthly for 6 months intrathecally. It is able to cross BBB with
moderate efficiency. The main side
Proprietary Preparations effects are on the bone marrow and
Mitomycin-C Kyowa (I) (Kyowa) Inj. 10mg/vial, gastrointestinal epithelium. It is one of
Tk.729.20/vial, Inj. 2mg/2ml, Tk.193.28/vial the important drugs in the treatment of
acute myeloid leukemia and, to a lesser
14.1.3 ANTIMETABOLITES extent, is used in chronic myelogenous
leukemia and non-Hodgkin’s lymphoma.
Antimetabolites are the chemothe- Using high dose cytarabin regimen,
rapeutic agents that includes folate additional toxic effects such as
antagonists, purine and pyrimedine intrahepatic cholestasis and central
analogue. nervous system toxicity are frequently
observed.
Methotrexate (antifolate) inhibits a key
enzyme in the thymidylate cycle, Fludarabine is a fluorinated nucleotide
dihydrofolate reductase (DHFR) analogue of the antiviral vidarabine (see
essential for DNA synthesis. section 1.4) which acts as a purine
Methotrexate is taken up into cells by the antagonist antimetabolite.It is used for its
folate carrier, and like folate, converted antineoblastic properties in the treatment
to the polyglutamate form. It is given of chronic lymphocytic leukaemia (CLL)
orally, intravenously, intramuscularly or after initial treatment with alkylating
intrathecally. Methotrexate is used in agent has failed. Fludarabine phosphate
childhood leukemia, non-Hodgkin’s is given by bolus injection or by IV
lymphoma, gestational trophoblastic infusion over 30 minutes in a usual dose
tumors, breast cancer, urinary bladder of 25 mg/m2 body-surface daily for 5
cancer, head neck cancer, lung cancer, consecutive days. Courses may be
gastrointestinal cancer and osteogenic repeated every 28 days. Fludarabine is
sarcoma. Intrathecal methotrxate is used generally well tolerated. Bone marrow
in prophylaxis of childhood acute suppression from fludarabine is dose-
leukemia and a therapy for established limiting, manifesting as leucopenia,
meningeal cancer or lymphoma. thrombocytopenia and anemia.
Methotrexate causes myelosuppression Myelosuppression can be severe and
and possible nephrotoxicity due to cumulative. CNS and pulmunary toxicity,
precipitation of the drug or metabolite in visual disturbances, heart failure, and
the renal tubule. It is contraindicated in autoimmune haemolytic anemia have
significant renal impairment because been reported rarely. Haematological
primarily the kidney excretes it. It may function should be monitored regularly;
cause damage to the gastrointestinal the dosage may need to be reduced, or
epithelium. It should be avoided in further courses delayed, if blood counts
severe hepatic impairment; should not indicate severe or persistent
be given in pleural effusion or ascites myelosuppression.
514
Cadribine is an effective but potentially FU is given usually intravenously

toxic drug given intravenous infusion for because absorption following oral
the treatment of hairy cell leukemia. It is administration is unpredictable. The toxic
also given in chronic lymphocytic effects of FU may be severe and
leukemia (CLL) in patients who have sometimes fatal which include bone
failed to respond to standard regimens marrow suppression, gastrointestinal
containing an alkylating agent. ulceration, bleeding, severe diarrhoea or
Myelosuppression may be severe and haemorrhage from any site, leucopenia,
serious neurotoxicity has been reported. thrombocytopenia, stomatitis and rarely
Gemcitabine is an analogue of cerebellar disturbances. The cytotoxic
cytrabine, which is metabolised effect of fluorouracil enhances with other
intracellularly to active diphosphate and cytotoxic drugs such as cisplatin,
triphosphate nucleosides, which inhibit methotrexate and with radiation (see
DNA synthesis. It is given in the also Appendix-2).
management of solid tumours including Capecitabine: which is metabolized to
those of lungs and pancreas. It is given fluorouracil, is given by mouth as
intravenously. Myelotoxicity reported to monotherapy in metastatic colorectal
be modest even at the high dose of cancer it has been shown to be of similar
Gemcitabine. Pulmonary oedema, efficacy as a combination of fluorouracil
alopecia, influenza-like symptoms, and folinic acid. Oral fluorinated
gastrointestinal side-effects, rashes and pyrimidine (a prodrug of 5FU) that
hypotension have also been reported. depends upon carboxyl esterase and
thymidine phosphorylase enzymees for
Severe toxicity, in the form of life- activation, is of interest because it may
threatening oesophagitis and be preferentially activated in tumors
pneumonitis has been seen in patients compared with normal tissues.
given radical radiotherapy. Gemcitabine Preferential activation at the tumor cell
should not be used concurrently with may increase the therapeutic index by
radiation therapy. Gemcitabine should producing higher cytotoxicity in colon
be used with caution in renal and hepatic cancer cells compared with non-
impairment. Haemolytic uraemic neoplastic cells. It is given in colorectal
syndrome has been reported rarely and cancer, breast cancer, and other
gemcitabine should be discontinued if gastrointestinal tract malignancy. Some
signs of microangiopathic haemolytic patients complain with a mild redness of
anemia occur. the palm of the hand or sole of the foot
Fluorouracil (FU), a pyrimidine which is known as “Hand foot syndrome”
analogue, is an antineoplastic that acts is easily reversible. Other than this no
as an antimetabolite to uracil.It interferes other side effects are observed.
with the synthesis of DNA; it can also Raltitrexed a thymidylate synthase
interfere with RNA synthesis. It also has inhibitor, is given intravenous infusion. It
immunosuppressant properties. is the front line treatment of advanced
FU is used alone or in combination in the colorectal cancer when FU and folinic
adjuvant treatment of breast and acid cannot be used. It is probably of
gastrointestinal cancer, and palliation of similar efficacy to FU. Raltitrexed is
inoperable malignant neoplasm, generally well tolerated, but can cause
especially those of gastrointestinal tract, marked myelosuppression and gastro-
breast, head and neck, genitourinary intestinal side-effects.
system and pancreas. FU is sometimes Mercaptopurine is a purine analogue,
used with folinic acid in colonic cancer produces cytotoxic actions by many
as adjuvant therapy and as first line different mechanisms and has several
therapy in advanced and metastatic inhibitory actions on de novo purine
colonic cancer. synthesis and they may themselves be
incorporated into DNA. It is well
515
absorbed when given orally. It is 100 mg/m2 IV or SC twice a week for 5

generally administered orally. days every 28 days.
It is inactivated by Xanthine Oxidase MAINTENANCE DOSE:
(XO). XO inhibitor, allopurinol (a purine  40-50 mg/m2 intrathecally every 4
analogue) inhibits the breakdown of days per week.
mercaptopurine and increases both its
effect and toxicity. Other purine  1,000 mg to 3,000mg/m 2 IV over 1
analogue, azathioprine, which gives rise hour every 12 hours for up to 12
to mercaptopurine in vivo, is used for doses.
non-malignant conditions such as
immunosuppression (see section Proprietary Preparations
14.2.2). The dose of both drugs should Cytarabine (I) (Choongwa) Inj. 100mg/5ml
Cytabin (Beacon), Inj. 100mg/5ml,
be reduced if the patient is receiving Tk.180/amp
allopurinol since it interferes with their
metabolism. Mercaptopurine is used
almost exclusively as maintenance FLUDARABINE PHOSPHATE
therapy for the acute leukemias.
Tioguanine (thioguanine) is given by Indications: B-cell chronic lymphocytic
mouth to induce remission in acute leukaemia, low grade Non-Hodgkin’s
myeloid leukemia. lymphoma, acute myeloid leukaemia-
Refractory and relapsing case.
CAPECITABINE Cautions: vaccination-during and after
treatment with fludarabine phosphate ,
vaccination with live vaccines should be
Indications: see notes above. avoided. renal impairment.
Side-effects: see section 14.1, Contraindication: hypersensitivity to the
important side-effect is hand foot active substance or to any of the
syndrome. excipients;Renal impairment with
Interactions: see Appendix-2. creatinine clearance < 30 ml/
min;Hemolyticanemia;Pregnancy(Pregna
Dose: 2500 mg/m2 per day in 2 to 3 ncy Category D);Lactation; below 18
divided doses for 2 weeks followed by 1 years of age
week rest, to be taken with food Side-effects: myelosuppression,
opportunistic Infections, cough, fever,
Proprietary Preparation fatigue, weakness, nausea, vomiting,
Xitabin(Beacon) Tab., 500 mg, Tk. 125/Tab.
Xeloda (I) (Roche), Tab., 500 mg, Tk. diarrhea, hematological disorders
350.29/Tab. Dose: 25 mg/m² body surface area
given daily for 5 consecutive days every
CYTARABINE 28 days by the Intravenous route for up
to 6 cycles.
Indications: acute myeloid leukemia
and, to a lesser extent, is used in chronic Fludara(I) (Genzyme), Inj., 50mg/2ml, Tk.
myelogenous leukemia and non- 7422/Vial
Hodgkin’s lymphoma.
Cautions: see section 14.1 and see FLUOROURACIL[ED]
notes above; hepatic impairment.
Side-effects: see section 14.1 and see Indications: see notes above
notes above. Cautions see section 14.1 and see
Dose: notes above
100-200 mg/m2/day continuous IV Caution: in handling-irritant to tissues
infusion for 5-10 consecutive days – Interactions: antibacterials such as
Induction or metronidazole inhibit the metabolism
516
(increase toxicity), filgrastim possibly Gemcitabin HEXAL (I) (Ebewe) Inj.,

exacerbates neutropenia (IV Infusion), 40mg/ml, 975.00/5mlvial, Tk.
3,937/25ml
Ulcer healing drugs such as cimetidine Gitrabin (I) (Actavis) Inj., (IV Infusion),
inhibits metabolism (increase plasma 200mg/vial,Tk.1848.08/Vial;1gm/vial
concentration) Tk.5850.50/vial
Side-effects: same as the side-effects
of cytotoxic drugs and see notes above MERCAPTOPURINE
2
Dose: systemic - 500 mg/m IV on days
Indications: acute lymphatic leukaemia
1-5 every 4 weeks. 450-600 mg/m2 IV
and acute non-lymphocytic leukemia.
weekly. 200-400 mg/m2 IV daily as a
May be useful treatments for chronic
continuous IV infusion. 1000 mg/m2 IV
myeloid leukaemia (CML), non-
daily for 4 days as a continuous IV
Hodgkin’s lymphoma, polycythaemia
infusion every 3-4 weeks
vera, inflammatory bowel disease and
Intra-cavitary- 500-1000 mg for psoriatic arthritis
pericardial effusion. 2000-3000 for
Cautions: same as the side-effects of
pleural or peritoneal effusion
cytotoxic drugs and see notes above;
2
Intra-arterial - 800-1200 mg/m as a reduce the dose in mild and moderate
continuous infusion on days 1-4 followed renal impairment; max. 2.5 mg in 24
by 600 mg/m2 as a continuous infusion hours and avoid in severe impairment
on days 5-21
Proprietary Preparation Side-effects: same as the side-effects
Fluroxan (Beacon), Inj., 250 mg, Tk. of cytotoxic drugs and see notes above
60.00/Vial; 500 mg, Tk. 100.00/Vial Dose: oral dose is 70 to 100 mg/m2/day
(by mouth 2.5 mg/kg daily); 75% of the
GEMCITABINE standard dose to be reduced if
allopurinol is co-administered. A
Indications: advanced pancreatic common IV dose is 500-1000 mg/m2/day
cancer: It may be useful in metastatic for 2-3 days. Dose adjustment of 6-MP
breast cancer administered by IV is not necessary with
Cautions: see section 14.1 and see concomitant administration of allopurinol
notes above
Side-effects: see section 14.1 and see Leukin (Beacon) Tab. 50 mg.Tk. 20/Tab.
notes above Puri Nethol (I) (GSK), Tab. 50 mg,
Dose: IV 1 g/m2 over a period of 30 Tk.40.76/Tab.
minutes once weekly for 7 weeks
followed by 1 week rest. Subsequent METHOTREXATE [ED]
courses of treatment are administered at
the dose of 1 g/m2 per week for 3 weeks Indications: chroriocorcinoma, hydatidi-
followed by 1-week rest form mole, all acute lymphocytic
leukaemia, prophylaxis and treatment of
Proprietary Preparations meningeal lymphocytic leukemia, breast
Gemoxen (Beacon), Inj., (IV Infusion), cancer, epidermal tumors of the head
40mg/ml Tk. 5,000/25mlVial; Tk. 1,400/5ml and neck, lung cancer, non-Hodgkin’s
Vial lymphoma, T-Cell lymphoma, psoriasis
Gemcitin (Techno), Inj., (IV Infusion),
40mg/ml, Tk. 7,287.50/25ml Vial; 200 mg/5ml, and rheumatoid arthritis (second or third
Tk.1,987.50/Vial line treatment). Methotrexate may be a
Gemcitabin medac(I) (Medac) Inj., useful treatment for multiple myeloma,
(IV Infusion), 200mg/vial, Tk.2,482.81/Vial; rhabdomyosarcoma and cancer of the
100mg/vial, Tk.12,411.03/vial bladder, brain, cervix, oesophagus,
Gemzar(Lilly)Inj., (IV Infusion), 200mg/vial, kidney, ovary, prostate, stomach and
Tk.2,478.34/Vial; 1g/vial, Tk.8671.92/vial testes
517
Cautions: see section 14.1 and notes Trexonate (Beacon), Tab. , 10 mg, Tk.
above; hepatic and renal impairment 15/Tab.; Tab., 2.5 mg, Tk. 5/Tab.; Inj., 50 mg,
Tk.130/amp.
Interactions: analgesics such as aspirin
reduce the excretion, avoid concomitant RALTITREXED
use of azapropazone, diclofenac,
ibuprofen, indomethacin, ketoprofen,
Indications: advanced colorectal cancer
meloxicam, naproxen and
Caution: hepatic and renal impairment
phenylbutazone and probably other
Contraindication: pregnancy and
NSAIDs increase the risk of toxicity (see
breast feeding
also Appendix-2 and notes below).
Side-effect: myclosppression and
Antibacterials such as co- trimoxazole
gastrointestinal disturbance
and trimethoprim increase the antifolate
effect of methotrexate, penicillin and Interaction: see Appendix-2
sulphonamides decrease the excretion Dose: consult with oncologist
of methotrexate and increase the risk of
toxicity. Generic Preparation
Antiepileptics such as phenytoin Injection 2mg/vial
increase the antifolate effect and thus
increase the toxicity. 14.1.4 VINCA ALKALOIDS AND
ETOPOSIDE
Antimalarial such as pyrimethamine
increase the antifolate effect.
The vinca alkaloids, Vincristine,
Ciclosporin increase the toxicity. vinblastine and vindesine are used to
Corticosteroids increase the risk of treat the acute leukaemias, lymphomas
haematological toxicity. and some solid tumors (eg. Breast and
Uricosuric-probenecid reduces the lung cancer). These naturally occurring
excretion of methotrexate and increases or semisynthetic compounds are derived
the risk of toxicity. from periwinkle plant. Vincristine,
vinblastine, vindesine, has been recently
Side-effects: same as the side-effects introduced. Vinorelbine are common
of cytotoxic drugs and notes above. vinka alkaloids used for different
Dose: oral doses up to 40mg/m 2 are well malignant conditions. They act by
absorbed. Parenteral doses vary from binding to tubulin and inhibit mitosis at
20-40 mg/m2 every 1 to 2 weeks to 200 metaphase. They are given by
to 500 mg/m2 every 2 to 4 weeks intravenous injection. The drugs are
As adjuvant treatment for osteosarcoma, rapidly sequestered in cells, particularly
doses of 12,000 to 15,000 mg/m2 have the white blood cells and platelets.
been given with leucovorin rescue the Vincristine has a longer life than other
usual adult intrathecal dose is 10 to 15 vinca alkaloids. The vinca alkaloids are
mg in 7 to 15 ml of preservative free relatively non-toxic. Myelosuppression is
saline. Doses greater than 80 mg/week the dose limiting side-effect of
should be accompanied by leucovoria vinblastine, vindesine and vinorelbine.
rescue Vincristine has a very mild
myelosuppressive activity, but causes
Proprietary Preparations paresthesia (sensory changes) and
G-Methotrexate (Gonoshasthaya), Tab., neuromuscular abnormalities fairly
2.5mg, Tk. 4.00/Tab. frequently. Motor weakness can occur
Methotrax (Delta), Tab., 10 mg, Tk. 15/Tab.; and increasing motor weakness calls for
Tab. , 2.5 mg, Tk. 5.00/Tab. discontinuation of treatment with these
Methox (Popular), Tab., 10 mg, Tk. drugs. Vinblastin is less neurotoxic but
15.06/Tab.;Tab., 2.5 mg, Tk. 5.52/Tab.
Metorax (Renata), Tab., 2.5 mg, Tk. 5.50/Tab.
causes leucopenia, while vindesine has
Mtrex(Techno), Inj., 50 mg, Tk 110/amp. both moderate myelotoxicity and
neurotoxicity.
518
Etoposide is the semisynthetic Cautions: and notes above; hepatic

derivative from mandrake root. It may be impairment. Caution in handling; (see
given orally or by slow intravenous under section 14.1)
infusions. Etoposide usually given daily Contraindications: intrathecal injection
for 3-5 days and courses should not be
repeated more frequently than at Side-effects: see under section 14.1
intervals of 21 days. It has particularly and notes above; irritant to tissue
useful activity in small cell carcinoma of Dose: 6 to 10mg/m 2 every 2 to 4 weeks
bronchus, the lymphomas and testicular in combination with other drugs
cancer. It may inhibit mitochondrial
function of nucleoside transport, as well Generic Preparations
as to an effect on topoisomerase II. Injection 10mg/10ml vial
Toxic effects include myelosuppression
and hair loss. Nausea and vomiting are VINCRISTINE SULPHATE[ED]
also common.
Indications: vincristine is an essential
ETOPOSIDE part of combination chemotherapy
regimens for ALL and play an important
Indications: particularly useful in lung role in the treatment of both Hodgkin’s
cancer, testicular and ovarian cancer, and non Hodgkin’s lymphomas and
gestational choriocarcinoma, Hodgkin’s certain other tumors
and non Hodgkin’s lymphomas, acute Cautions: Same as the side-effects of
myelogenous leukaemia, acute cytotoxic drugs and notes above; hepatic
myelomonocytic leukaemia, Kaposi’s impairment. Caution in handling
sarcoma, neuroblastoma, Ewing’s
Contraindications: Intrathecal injection
sarcoma, Wilm’s tumor and
rhabdomyosarcoma, cancer of breast, Side-effects: same as the side-effects
bladder and prostate. of cytotoxic drugs and notes above;
irritant to tissue
Cautions : same as the side-effects of
cytotoxic drugs and notes above Interactions: see Appendix-2
Contraindications: severe hepatic Dose: commonly used doses range from
impairment 0.5 to 1.4 mg/m2 every 1 to 4 weeks.
Continuous infusion regimens of 0.5 mg
Side-effects: myelosuppression,
to 0.5 mg/m2/day for 4 days have been
alopecia, peripheral neuropathy; it is also
used
irritant to tissue. Nausea and vomiting
Dose: 120-240 mg/m2/day for 3 to 5 Proprietary Preparations
days; given orally Criston (Beacon), Inj., 1 mg/Vial, Tk.
350.00/Vial ; 2 mg/Vial, Tk. 580.00/Vial
Proprietary Preparations Vincrist (Techno ), Inj., 1 mg/Vial, Tk.
Topoxin (Beacon), Inj.,100mg/vial,Tk. 400/Vial 460.00/Vial
Eposid (Techno), Inj., 100 mg/vial, Tk.530/Vial Vincristine(I)(Phamachemie) 1 mg/Vial, Tk.
Eposin(I)(Pharmachemie), Inj., 100mg/vial, Tk. 371.95/Vial ; 2 mg/Vial, Tk. 526.92/Vial
584.07/Vial
VINORELBINE
VINBLASTINE SULPHATE [ED]
Indications: see notes above
Indications: advanced Hodgkin’s Cautions: see section 14.1 and notes
lymphomas and also to treat the above
carcinomas of bladder, breast, Kaposi’s
Side effects: see section 14.1 and
sarcoma and certain other malignant
notes above
conditions, mycosis fungoides
Dose: Consult with oncologist
519
prostate cancer and for pancreatic

Proprietary Preparations cancer. It is a reversible tyrosine kinase
Vinorelbin Sandoz(I) (Ebewe), Inj (I.V inhibitor, which acts on the epidermal
Infusion)10 mg/ ml, Tk. 1247.00/Vial; growth factor receptor
4,370.00/5 ml, Vial Note: Erlotinib monotherapy is not
Vinorelbin Actavis(I) (Actavis), Inj(I.V
Infusion), 10 mg/ ml, Tk. 10246.93/5mlVial;
recommended for maintenance
treatment in people with locally
advanced or metastatic non-small-cell
14.1.5 OTHER ANTINEOPLASTIC
lung cancer who have stable disease
DRUGS
after platinum-based first line
chemotherapy.
Amscarine acts by intercalation with Everolimus is a protein kinase inhibitor.
DNA and inhibition of nucleic acid It is used to treat advanced renal cell
synthesis. It is used for the induction and carcinoma that has already been treated
maintenance of remission in adult acute unsuccessfully with other medications. It
lymphatic leukaemias, particularly acute is also used to treat a certain type of
non-lymphoblastic leukaemia. Amsacrine advanced breast cancer that has already
has cardiotoxic effects similar to those of been treated with at least one other
doxorubicin and it is poorly absorbed medication.
following oral administration. Side-effects Imatinib is a protein tyrosine kinase
include bone marrow depression and inhibitor, which is licensed for the
mucositis; cardiac arrhythmia may occur treatment of chronic myeloid leukaemia,
especially in patients with pre-existing in chronic phase after failure of interferon
hypokalaemia. alfa, or in accelerated phase or in blast
Altretamine is recently been licensed for crisis. The most frequent side effects of
the treatment of advanced ovarian imatinib are nausea, vomiting, diarrhea,
cancer where other regimen has failed. oedema, muscle pain and headache.
Altretamine is given orally and should be
discontinued if dose reduction fails to Nilotinib a tyrosine kinase inhibitor,
stabilize symptoms of neurological used for the treatment of newly
toxicity. Prolonged or high dose therapy diagnosed adult patients with
may be associated with peripheral and Philadelphia chromosome positive
central neurotoxicity and regular chronic myeloid leukemia in chronic
neurological examination is to be phase and also for the treatment of
recommended. Other side-effects chronic phase and accelerated phase in
include rash, renal and hepatic toxicity. adult patients resistant to or intolerant to
prior therapy that included imatinib.
Crisantaspase is the enzyme Sorafenib is a tyrosine kinase inhibitor.
asparaginase produced by Erwinia Sorafenib is used to treat advanced
chrysanthemi. It is given IM or S/C renal cell carcinoma Sorafenib is also
exclusively in Acute Lymphoblastic used to treat hepatocellular carcinoma
Leukaemia. Side-effects include nausea that cannot be treated with surgery and a
and vomiting and can cause certain type of thyroid cancer that has
anaphylactic reactions, CNS depression, spread to other parts of the body and
and liver damage. cannot be treated with radioactive iodine.
Erlotinib is used for treatment of Sunitinib Sunitinib is a type of targeted
patients with metastatic or locally therapy known as a tyrosine kinase
advanced non-small cell lung cancer inhibitor. This drug is used to treat
who have failed at least one previous advanced kidney cancer. It is also used
round of chemotherapy. It also is used in gastrointestinal stromal tumor , after
for maintenance of NSCLC that has not failure of imatinib, and for the treatment
progressed after four cycles of platinum- of unresectable or metastatic pancreatic
based first line chemotherapy. Erlotinib neuroendocrine tumour .
is combined with gemcitabine to treat
advanced unresectable metastatic
520
ALTRETAMINE Temozolomide is structurally related to

decarbazine and is licensed for the
Indications: see notes above second line treatment of malignant
glioma. It is an oral preparation.
Cautions: hepatic and renal impairment;
to be careful in handling (see section
DACARBAZINE
14.1 and notes above)
Side-effects: see section 14.1 and Indication: see notes above.
notes above
2
Caution: same as the side-effects of
Dose : 260 mg/m /day in 4 divided dose cytotoxic drugs and notes above; hepatic
(after meals and at bedtime) for 14 days and renal impairment ,pregnancy, breast
to 21 days of a 28 day cycle; given for up feeding
to 12 cycle
Generic Preparation of cytotoxic drugs and notes above;
Capsule 100mg rarely liver necrosis due to hepatic vein
thrombosis; irritant to skin and tissues
BORTEZOMIB Dose: it is given IV in doses of 150-250
mg/m2/day for 5 days, to be repeated at
Indication: relapsed multiple myeloma intervals of 4 weeks, or 250 mg/m2 body
and mantle cell lymphoma surface daily for 5 days, to be repeated
Cautions: pregnancy, liver disease, at intervals of 3 weeks
kidney disease
Contraindication: pregnancy Proprietary Preparations
Decarbazine (I) (Mayane), Inj. 200 mg/20 ml.
Side-effects: peripheral neuropathy, Tk.1126.96/20ml vial
myelosuppression, neutropenia, Decarbazine Medac(I) (Medac), Inj.,
thrombocytopenia, asthenia. 200mg/ vial,Tk.7962.35/vial
Dose: 1.3 mg/m2 (with or without
dexamethasone) administered by ERLOTINIB
intravenous bolus on days 1,4,8, and 11
of a 21-day cycle for a maximum of eight Indications: see notes above
Cautions: see section 14.1 and notes
cycles in heavily pretreated patients with
above;.renal impairment; hepatic
relapsed/refractory multiple myeloma. impairment; pregnancy & breast feeding.
Generic Preparation of cytotoxic drugs and notes above.
Injection 3.5mg/vial Dose : non-small cell lung cancer, 150
mg once daily. Pancreatic cancer, 100
DACARBAZINE AND TEMOZOLOMIDE mg once daily in combination with
gemcitabine
Dacarbazine is a cell cycle non-specific
antineoplastic which may function as an Proprietary Preparations
alkylating agent after it has been Erlonix (Beacon), Tab. , 100 mg, Tk.
activated in liver and is used mainly to 600.00/Tab.; 150 mg, Tk. 750.00/Tab.
Tarceva(I) (Roche), Tab., 150 mg, Tk.
treat metastatic malignant melanoma, in
5,091.13/Tab.; 100 mg, Tk. 4,168.21/Tab.
combination regimen for the treatment of Tercenib (Techno), Cap. , 150 mg, Tk.
soft tissue sarcoma, Hodgkin’s disease. 750.00/Cap.; 100 mg, Tk. 650.00/Cap.
It is given intravenously. The
predominant side-effects are
myelosuppression & severe nausea,
vomiting.
521
EVEROLIMUS REA
Hydroxycarbamide (hydroxyurea) is a
Indications: advanced kidney cancer, urea analogue that inhibits ribonucle-
prevention of organ rejection after renal otide reductase, thus interfering DNA.
and kidney transplant, breast cancer in The drug is given orally & is mainly
post-menopausal women with advanced licensed for the treatment of chronic
hormone-receptor positive myeloid leukaemia. It has the usual
Cautions: hepatic impairment, renal unwanted effects; bone marrow
impairment, pregnancy, breast feeding depression being significant.
Side effects: change in ability to taste
food, dry mouth, weakness, difficulty HYDRPXY CARBAMIDE
falling asleep, nose bleed, muscle
cramps Indication: see notes above
Dose: renal cell carcinoma, Cautions, Side-effect : see section 14.1
neuroendocrine tumours of pancreatic Contra-indications: pregnancy & breast
origin, hormone-receptor-positive breast feeding
cancer. ADULT over 18 years, 10mg Dose: cosult with oncologist
once daily
Proprietary Preparations:
Note: for subependymal giant cell
Hydrea(I)(Squibb),Cap.500mg, Tk.19.83/Cap
astrocytoma or renal angiomyolipoma Hydronix(Beacon),Cap. 500mg, Tk.15.00/Cap
associated with tuberous sclerosis
complex; consult product literature IMATINIB
Afinitor(I) (Novartis), Tab., 5 mg, Tk. Indication: see notes above.
5813.00/Tab.; 10 mg, Tk. 8943.00/Tab.; Cautions: cardiac disease; risk factors
Certican(I) (Novartis), Tab., 0.25 mg, Tk. for heart failure; history of renal failure;
125.00/Tab.; 0.50 mg, Tk. 250.00/Tab monitor for fluid retention; monitor liver
Xevirol(Beacon), Tab., 5 mg, Tk. 66.60/Tab.; function ; monitor growth in children (see
10 mg, Tk. 100.00/Tab.; section 14.1)
Side-effects: see section 14.1 and
GEFITINIB
notes above.
Dose: 400 mg/day till the disease
Indication: Non-small cell lung cancer persists (Literature advised for at least
(NSCLC). one year)
Cautions: breast-feeding, interstitial
lung disease (ILD), hepatotoxicity and Proprietary Preparations
liver impairment Imanix (Beacon), Tab. , 100 mg, Tk.
Contraindication: pregnancy and 100.00/Tab.; 400 mg, Tk. 375.00/Tab.
breast-feeding (must be discontinued Enliven (Orion ), Cap, 100 mg, Tk.
while receiving Gefitinib therapy) 125.47/Cap.
Side effects: anorexia mild or moderate, Glivec(I) (Novartis), Cap. 100 mg, Tk.
conjunctivitis, blepharitis, and dry eye, 1666.00/Cap.
corneal erosion, Keratitis (0.12%),
haemorrhage, diarrhoea, vomiting, LAPATINIB
hepatobiliary disorders, skin reactions,
nail disorder, cutaneous vasculitis, Indications: metastatic breast cancer
proteinuria, cystitis and other solid tumors. It is used in
Dose: 250mg tablet once a day combination therapy for HER2-positive
breast cancer.
Proprietary Preparation Cautions: hepatotoxicity, pregnancy
Gefinix (Beacon), Tab. 250 mg, Tk.250/Tab.
category D, renal impairement
Contraindication: same as that of
HYDROXYCARBAMIDE/HYDROXYU cautions
522
Side effects: fast or pounding heart Side effects: changes in hair colour,
beats, extreme dizziness or tired feeling, hypertension which usually occurs
feeling like you might pass out, severe during the first few weeks of treatment,
diarrhea, dry cough, feeling short of appetite loss, hyperglycaemia,
breath, white patches or sores inside hypocalcaemia, hypomagnesemia,
mouth or on lips, nose bleeding (see hypophosphatemia, increased AST, ALT
and protein in the urine, oedema, rash,
section 14.1) fatigue, and myelosuppression.
Dose: 1,250 mg given orally once daily
Interactions:see Appendix -2
on Days 1-21 continuously in
Dose: 800 mg orally once daily without
combination with capecitabine 2,000
food (at least 1 hour before or 2 hours
mg/m2 /day (administered orally in 2
after a meal). Baseline moderate hepatic
doses approximately 12 hours apart) on
impairment – 200 mg orally once daily.
Days 1-14 in a repeating 21-day cycle.
Proprietary Preparation Votrient(I) (GSK) Tab.,800 mg Tk.625.69
Tykerb(I) (GSK),Tab., 250 mg TK.356.59/Tab
SORAFENIB
NILOTINIB
Indications: see notes above Indications: see notes above

Cautions: prolongs the QT interval; Caution: major surgical procedures,
concomitant use of drugs that prolong cardiac ischaemia, susceptibility to QT-
QT interval; hypokalemia, interval prolongation, hepatic
hypomagnesemia, or long QT impairment, pregnancy and breast-
syndrome feeding
Side effects: headache with chest Side-effects: decreased blood flow to
pain and severe dizziness, fainting, the heart and heart attack, bleeding
fast or pounding heartbeats; fever, problems,high blood pressure, hand-foot
chills, body aches, flu symptoms, skin reaction,Interstitial lung disease
sores in mouth and throat; blood in reversible thyroid dysfunction and
urine or stools; severe pain in upper Stevens-Johnson syndrome
stomach spreading to back; QT- interval Dose: ADULT over 18 years, 400 mg
prolongation; hypertension, oedema twice daily
Dose: consult product literature
Soranix (Beacon),Tab. 200mg,Tk.300.00/Tab.
Tasigna(I) (Novartis), Cap. 200 mg,
Tk.3040/Cap. SUNITINIB
PAZOPANIB Indications: see notes above

Cautions: increased risk of bleeding;
Indications: renal cell carcinoma and monitor for thyroid dysfunction;
soft tissue sarcoma congestive heart failure, high blood
Cautions: hypertension, including pressure, QT-interval prolongation;
hypertensive crisis , thrombotic consider dental check-up before initiating
microangiopathy; thrombocytopenic treatment, pregnancy and breast-feeding
purpura, hemolytic uremic syndrome; Side-effects: fatigue, hand-foot skin
decreased LVEF and congestive heart reaction, hypertension, paraesthesia,
failure hypothyroidism, arthralgia, increased
Contraindications: Same as that of lacrimation, epistaxis
cautions, not recommended in patients
with severe hepatic impairment
523
Dose: 50 mg once daily for patient basis and it is better tolerable

gastrointestinal stromal tumor and than cisplatin. The dose of carboplatin
advanced renal cell carcinoma is determined according to the renal
function rather than the body surface
Proprietary Preparation area. Though the myelosuppression is
Sunitix (Beacon), Cap. 50 mg, Tk. 2000/Cap. more severe than cisplatin but the
nephrotoxicity or ototoxicity with
TEMOZOLOMIDE carboplatin is less severe.
Oxaliplatin is administered intraven-
Indication: malignant glioma. ously for the treatment of metastatic
Cautions: same as the side-effects of colorectal cancer in combination with
cytotoxic drugs and notes above; hepatic flourouracil and folinic acid. Along with
and renal impairment; caution in sensory peripheral neuropathy which id
handling dose limiting other side effects eg. GIT
Contraindication: CHILD under 3 years disturbance, ototoxicity, myelosuppre-
not recommended ssion are also common. Manufacturers
advise for close monitoring of the renal
Side-effects: see notes above functions.
Dose: consult product literature
Proprietary Preparations: CARBOPLATIN

Temonix (Beacon), Cap. , 100 mg, Tk.
600.00/Cap.; 250 mg, Tk. 1,300.00/Cap. Indications: see notes above
Zolomide (Techno), Cap. , 100 mg, Tk. Cautions: see section 14.1 and notes
650.00/Cap.; 250 mg, Tk. 1,500.00/Cap
above; renal impairment
Interactions: antibacterials such as
PLATINUM COMPOUNDS aminoglycosides, vancomycin and
capreomycin increase the risk of
The platinum compounds are complexes nephrotoxicity and possibly ototoxicity;
of platinum with ligands which can be diuretics increase the risk of
displaced by nucleophilic (electron rich) nephrotoxicity and ototoxicity.
atoms to form strong bonds with Side-effects: see section 14.1 and
covalent characteristics. Thus, like the notes above
alkylating agents, the platinum agents Doses: common IV dose is 360 to 400
form strong chemical bonds with thiol mg/m2 every 4 weeks. Doses of 400 to
sulfurs and amino nitrogens in proteins 550 mg/m2 have been given. Carboplatin
and nucleic acids. can also been administered in higher
Cisplatin requires a “Day-care setting” doses (e.g. 1500 mg/m2) in combination
and is given intravenously. It is of value with other antineoplastic drugs
in patients with metastatic germ cell The dose of carboplatin, based on target
tumors (Teratoma, seminoma). It can AUC, is calculated using the following
also be used in bladder, lung, upper GIT formula:
and ovarian cancer though for ovarian Dose (total mg)=Target AUC X (GFR +
cancer carboplatin is more preferable. 25)
Cisplatin requires intensive intravenous The patient’s creatinine clearance, in
hydration and treatment may be ml/minute, is often used in place of GFR.
complicated by severe nausea and A target AUC of 6 to 7 is often used
vomiting. This is generally toxic giving depending on the patient’s prior
rise to nephrotoxicity, ototoxicity, therapies and drug(s) that will be used in
peripheral neuropathy. combination with carboplatin. A target
Carboplatin has activity equivalent to AUC of 4 to 6 may be appropriate for
that of cisplatin but used specially in patients who have received extensive
ovarian cancer and lung cancer prior treatment, and a higher target AUC
(Particularly small cell type). It is may be appropriate for previously
administered intravenously on an out untreated patients
524
Contraindications: peripheral
Proprietary Preparations neuropathy and functional impairment
Carboplat (Beacon), Inj.,(I.V infusion) Side-effects: see section14.1 and notes
10mg/ml, Tk. 1,400.00/15mlVial ; Tk. above
3,800.00/45 ml Vial Dose: consult with oncologist
Carbotin (Techno ), Inj. (I.V infusion)10mg/ml,
Tk. 4,637.50/45ml; Tk.1,550.00/15mlVial
Carboplatin HEXAL(I) (Hexel), Inj. (I.V Proprietary Preparations
infusion) 10mg/ml ,Tk. 1,166.00/15 ml Vial; Eloxatin(I) (Aventis), Inj. 50 mg/Vial, Tk.
Tk. 3,069.00/45 ml Vial; Tk. 423.00/5 ml Vial 6230.74/Vial
Carboplatin sindan(I) (Sindan) Inj. (I.V Oxaliplatin medac(I) (Medac) , Inj., 100
infusion) 10mg/ml, Tk.4146.14/45ml vial; Tk. mg/vial, Tk. 5387.32/vial
5156.47/60ml vial Oxalotin (Techno), Inj., 100 mg/vial, Tk.
7,900.00/vial ;50 mg/vial,Tk. 5,962.50/vial
Xaloplat (Beacon), Inj., 100 mg/vial, Tk.
CISPLATIN[ED] 5,500.00/vial; 50 mg/vial, Tk. 3,000.00/vial
Sindaoxplatin(I) (Sindan), Inj., 50 mg/Vial, Tk.
Indications: same as notes above 4377.00/vial
Cautions: see section 14.1 and notes
above; renal impairment; to be PROCARBAZINE[ED]
monitored renal function and
haemoglobin parameter Procarbazine is mainly used in the
Interactions: antibacterials such as treatment of Hodgkin’s disease, with
aminoglycosides, vancomycin and other combination eg. MOPP (Mustine,
capreomycin increase the risk of Oncovin, Procarbazine and Predniso-
nephrotoxicity and possibly ototoxicity; lone). It inhibits DNA and RNA synthesis
diuretics increase the risk of and interferes with mitosis at interphase.
nephrotoxicity and ototoxicity Its effects may be due to the production
Side-effects: see section 14.1 and of active metabolites. It is given orally.
notes above Usual side-effects includes nausea,
Dose: doses may vary from 20 to 40 hypertension, tachycardia, diplopia,
mg/m2/day for 3 to 5 days every 3 to 4 photophobia, myelosuppression and skin
weeks or from 20-120 mg/m2 given as a rash Immediate cessation of treatment is
single dose every 3-4 weeks intra required if rash appears.
peritoneal dose of 100 to 270 mg/m2
have been given in combination with IV PROCARBAZINE [ED]
sodium thiosulfate
Indications: same as notes above.
Proprietary Preparations Cautions: see section 14.1and notes
Cesalin (Techno), Inj. (I.V infusion) , Tk.
above; renal impairment; reduce the
225.00/10mgVial;Tk. 1,060.00/50mgVial
Cisplatin HEXAL PI(I) (Hexel), Inj. (I.V dose in moderate impairment
infusion) Tk. 313.00/20 ml Vial ; 50 mg/100ml, Interactions: alcohol ingestion may
Tk. 987.00/100 ml Vial cause a disulfiram like reaction; it can
Platinex (Beacon), Inj. (I.V infusion) , Tk. cause hypertension, because it is a
250.00/10mgVial; Tk. 815.00/50mgVial weak MAOI. see also Appendix-2
Sinplatin(I) (Actavis), Inj. (I.V infusion) 50 Side-effects: see section 14.1 and
mg/vial,Tk.1114.47/50mlVial;Tk.370.00/10mlvi
notes above
al
Dose : initially 50 mg daily, increased by
50 mg daily to 250-300 mg daily, in
OXALIPLTIN divided doses; maintenance (on
remission) 50-150 mg daily to cumulative
Indications: metastatic colorectal total of at least 6g
cancer in combination with FU and folinic
acid Generic Preparation
Cautions: renal impairment Capsule 50 mg.
525
TAXENES CABAZITAXEL
Docetaxel, though recently been Indications: In combination with

licensed for initial chemotherapy with prednisone, for the treatment of patients
doxorubicine for advanced breast with hormone-refractory metastatic
cancer, it’s main use was in the prostate cancer (mHRPC) previously
treatment of advanced or metastatic treated with a docetaxel-containing
breast cancer and non-small cell lung treatment regimen
cancer. It is the second generation Cautions: severe hypersensitivity can
taxene. It acts by enhancing formation occur and may include generalized rash/
and stabilization of microtubules. erythema, hypotension and
Antineoplastic effect may result from bronchospasm. Discontinue cabazitaxel
non-functional tubules or altered tubulin immediately if severe reactions occur
microtubule equilibrium. Mitotic arrest is and administer appropriate therapy
seen and is associated with accumulated Contraindications: in patients with
polymerized microtubules. Dose limiting neutrophil counts of ≤1,500 cells/mm3; a
factor for Docetaxel is neutropenia. history of severe hypersensitivity
Severe (grade 4) neutropenia is common reactions to cabazitaxel or to other drugs
among patients who have neutropenic formulated with polysorbate 80
fever. Nausea and vomiting are Side-effects: The most common (_10%)
common, but brief. Fluid retention grade 1–4 adverse reactions were
syndrome is common and cumulative. It anemia, leukopenia, neutropenia,
can be reduced to occasional frequency thrombocytopenia, diarrhea, fatigue,
by prophylactic steroids. Severe nausea, vomiting, constipation, asthenia,
hypersensitivity reactions with flushing, abdominal pain, hematuria, back pain,
hypotension with or without dyspnoea. anorexia, peripheral neuropathy, pyrexia,
pre-medication with dexamethasone, 8 dyspnea, dysgeusia, dyspepsia, cough,
mg PO twice daily for 5 days starting 1 arthralgia, and alopecia. The most
day before docetaxel limits the frequency common (_5%) grade 3–4 adverse
and severity of hypersensitivity. reactions in patients who received
Paclitaxel is the first drug of the new cabazitaxel were neutropenia,
class known as Taxanes. It is given leukopenia, anemia, febrile neutropenia,
intravenous infusion. Paclitaxel along diarrhea, fatigue, and asthenia
with carboplatin or cisplatin is the Dose 25 mg/m² as a 1-hour IV every 3
treatment of choice for ovarian cancer weeks, in combination with oral
(NICE guideline). Paclitaxel is also used prednisone 10 mg administered daily
in second line treatment of metastatic
breast cancer. Some source also claim Proprietary Preparation
for it’s usefulness in non-small cell lung Jevtana(I) (Sanofi), Inj., 60 mg/1.5 ml, Tk.
cancer. Routine pre medication with a 142687/Vial
corticosteroid and an antihistamine to
prevent severe hypersensitivity reaction DOCETAXEL
is recommended. Hypersensitivity
reactions may occur rarely; although Indications: breast cancer, non-small
more commonly only bradycardia or cell lung cancer, gastric cancer, head
asymptomatic hypotension may occur. and neck cancer, ovarian cancer; see
Along with these some complains of also the notes above
myelosuppression, peripheral Cautions: same as the side-effects of
neuropathy and cardiac conduction cytotoxic drugs; hepatic impairment,
defects with arrhythmias (which are monitor liver function - dose reduced
nearly asymptomatic). It also causes according to liver enzymes; avoid in
alopecia, muscle pain, nausea and severe hepatic impairment
vomiting from mild to moderate.
526
Contraindications: patients with serious Xelpac (Beacon), Inj(I.V Infusion), 100mg/Vial,

bone marrow depression, complication Tk. 4,500.00/Vial ; 30 mg/Vial, Tk.
of infection, suspecting of infection 1,700.00/Vial; 300 mg/Vial, Tk. 9,900.00/Vial
Interactions: erythromycin, ketocona-
zole, ciclosporin may cause possible TOPOISOMERASE I INHIBITORS
interactions; see also Appendix-2
Side-effects: same as the side-effects Irinotecan and topotecan are the
of cytotoxic drugs recently introduced anticancer drugs
Dose: ADULT dose is 60-100 mg/m 2 which inhibit topoisomerase I, an
(body surface area), IV drip infused over enzyme involved in DNA replication. In
1 hour once a day at intervals of 3-4 addition to dose limiting
weeks myelosuppression, side-effects of
Proprietary Preparations irinotecan and topotecan include
Docexan (Beacon), Inj., 20 mg/0.5 ml, Tk. gastrointestinal effects, asthenia,
3,200.00/Vial;80 mg/2 ml, Tk. 11,000.00/Vial alopecia and anorexia.
Docetex (Techno), Inj., 20 mg/0.5 ml, Tk. Irinotecan, a semisynthetic derivative of
5,000.00/Vial ; 80 mg/2 ml, Tk. 18,000.00/Vial
camptothecins is potent inhibitor of
Taxotere(I) (Sanofi), Tab. 20 mg, Inj. Tk.
6991.00/Vial topoisomerase I, an enzyme essential
for effective replication and transcription,
is given by intravenous infusion in
PACLITAXEL
carcinoma of the colon or rectum in
combination with fluorouracil and folinic
Indications: primary ovarian cancer acid or when flouorouracil failed.
(advanced or residual disease following Topotecan is given by intravenous
laparotomy) in combination with infusion in metastatic ovarian cancer
cisplatin; metastatic ovarian cancer when first line or subsequent therapy
where standard platinum-containing has failed.
therapy has failed; advanced or
metastatic breast cancer (in combination
IRINOTECAN HYDROCHLORIDE
with trastuzumab) when an anthracycline
not appropriate; metastatic breast
carcinoma where standard Indications: carcinoma of the colon or
anthracycline-containing therapy has rectum in combination with fluorouracil
failed or is inappropriate; non small cell Cautions: see section 14.1 and notes
lung cancer (in combination with above; raised serum bilirubin
cisplatin) when surgery or radiation concentration. Avoid in severe hepatic
therapy not appropriate impairment
Cautions: see section 8.1 and notes Contraindications: chronic IBS, bowel
above. obstruction, plasma bilirubin
Interactions: see Appendix-1 concentration more than 1.5 times the
Contra-indications: see notes above upper limit of reference range; avoid
Side-effect: see notes above. conception for at lest 3 months after
cessation of treatment
Proprietary Preparations Side-effects: same as the side-effects
Paclitaxel Actavis(I) (Actavis), Inj(I.V Infusion), of cytotoxic drugs and notes above;
6mg/ ml, Tk. 5081.88/16.7 ml Vial; acute cholinergic syndrome and delayed
Tk.13855.01/43.33ml vial diarrhoea
Paclitaxel medac(I) (Medac) Inj(I.V Infusion), Dose : 350 mg/m2 administered as an IV
300 mg/Vial,Tk/13,552.94/Vial; 100 mg/16.7ml, infusion over a 30 to 90 minute period
Tk. 6,707.25/Vial; 30 mg/5 ml, Tk.2,647.69/Vial
every three weeks as single agent in
Paclitaxel Sandoz(I) (Ebewe), Inj(I.V Infusion),
100 mg/16.7 ml, Tk. 2,826.00/Vial; 30 mg/5 ml, 5FU refractory cases, and 180 mg/m 2 in
Tk. 1,205.00/Vial combination with 5FU and folinic acid as
Paclitex (Techno), Inj(I.V Infusion), 6 mg/ml, first line therapy
Tk. 2,650.00/5mlVial ; Tk. 11,500.00/50mlVial
527
Proprietary Preparations TRASTUZUMAB

Campto(I) (Pfizer), Inj. (IV infusion), 20 mg/ ml,
Tk. 11,957.63/5 ml Vial; Tk. 4985.59/5 ml Vial Indication: as a single agent is indicated
Irinotecan Sandoz(I) (Ebewe), Inj.(I.V for the treatment of metastatic breast
infusion), 20mg/ ml, Tk. 1,398.00/5 ml Vial ; cancer in HER2 over expressions
100 mg/5 ml, Tk. 2,800.00/5 ml Vial Cautions: history of hypertension,
Irinotecan medac(I) (Medac), Inj.(IV infusion),
pregnancy
100 mg/5 ml, Tk. 9,101.42/Vial ; 40mg/2 ml,
Tk. 4,137.01/Vial Contraindications: severe dyspnoea
Irinotesin(I)(Actavis), Inj. (IV infusion), and breast-feeding
20mg/ml, Tk.6326.38/5mlvial; Tk.2588.06/2ml Side-effects: chills, fever, anaphylaxis,
vial urticaria, angioedema, gastrointestinal
symptoms, asthenia, arthralgia,
TOPOTECAN
hypotension
Indications: metastatic Dose : 4 mg/kg IV as loading dose over
Cautions: renal impairment, pregnancy 90 min followed by 2 mg/kg over 30 min
and breast feeding. weekly
Contraindications: see notes above, Proprietary Preparations
hepatic impairment, pregnancy and Herceptin(I) (Roche), Inj., 440 mg/vial, Tk.
breast feeding 208766.54/Vial
Side-effects: see notes above and see Trastunix (Beacon), Inj., 440 mg/Vial, Tk.
sec.14.1 80,000.00/Vial
Dose:1.5 mg/m2/day for 5 days as single Zumab (Techno), Inj., 440 mg/Vial, Tk.
agent 1,26,000.00/Vial
Generic Preparations TRETINOIN

Injection 1mg/ml, 4ml vial
Tretinoin is licensed for the induction of
TRASTUZUMAB remission in acute promyelocytic
leukaemia. It is used in previously
Trastuzumab is a monoclonal antibody untreated patients as well as in those
that has recently introduced for the who have relapsed after standard
treatment of metastatic breast cancer in chemotherapy or who are refractory to it.
patients whose tumours overexpress The efficacy of All Trans Retinoic acid
the human epidermal growth factor (ATRA) in the treatment of Acute
receptor 2 (HER2). Trastuzumab Promyelocytic Leukemia (APL) was first
treatment should be reserved for demonstrated in 1988 in China & then in
patients who have previously received France, the USA & Japan. In APL
appropriate chemotherapy or in whom patients there is a translocation between
such treatment is inappropriate. chromosomes t(15, 17). In patient with
Administration should be monitored by a this (15;17) chromosome translocation,
specialist. As trastuazumab is a the trans retinoic acid has been used to
monoclonal antibody and is highly induce remission by causing
selective, it is important to done the differentiation of the malignant clone. In
receptor study (ER, PR, and HER2) many APL patients (25%) treated with
before prescribing trastazumab. Suitable vesanoid a syndrome occurs known as
patient selection is important for using RAS. The pathogenesis of RAS & the
Trastuzumab. The combination of relationship to the other biologic effects
trastuzumab with taxanes improves the seen with Vesanoid (RA) remains
efficacy in a wide range. Trastuzumab unclear. The description of a similar
should only be used in patients whose symptom complex in patients with APL
tumors have HER2 over expression who have not received RA has raised
the possibility that this syndrome is
directly related to the disease process.
At the first onset of RAS, a short course
of high dose steroid (Dexamethasone 10
528
mg iv, twice a day, for three or more 14.2. DRUGS AFFECTING THE
days) can effectively stop progression of IMMUNE RESPONSE
RAS. Vesanoid is highly teratogenic; so
contraindicated in pregnancy, and 14.2.1 ANTIPROLIFERATIVE
Nursing mothers. In many APL patient IMMUNOSUPPRESSANTS
treated with vesanoid a syndrom occurs 14.2.2 CORTICOSTEROIDS AND
known as RAS. If untreated, this may be OTHER
fatal. IMMUNOSUPPRESSANTS
14.2.3 RITUXIMAB
TRETINOIN
14.2.4 INTERFERONS
14.2.5 ALDESLEUKIN
Indication: acute promyelocytic 14.2.6 BCG IMMUNOTHERAPEUTICS
Leukaemia.
Caution: monitor Retinoic Acid
Syndrome IMMUNOSUPPRESSANT THERAPY
Interactions: see Appendix-2
Contraindication: pregnancy & Nursing Immunosuppressants are used to
mother as it is highly teratogenic suppress rejection of transplanted
Side-effects: RAS, acute respiratory organs and tissues (kidney, bone
distress, edema, hepatic or renal failure marrow etc.); to suppress graft-versus-
Dose: adult and child 45 mg/m2 daily in host disease in bone marrow
two divided doses. Duration of treatment transplants; to treat a variety of chronic
is 90 days inflammatory and auto-immune diseases
which includes ITP, some forms of
Proprietary Preparation Haemolytic Anaemia, GN, Myasthenia
Vesanoid(I) (R.P. Scherer), Cap. 10 mg, Tk. Gravis, SLE, Rheumatoid Arthritis, etc.
190.54/Cap.
PREGNANCY: Transplant patients
BEVACIZUMB maintained with azathioprine should not
discontinue it on becoming pregnant;
Indications: used in combination with because there is no evidence of
I.V 5FU based chemotherapy, first line azathioprine’s teratogenicity. There is
treatment of patient with metastatic less experience of ciclosporin in
carcinoma of colon and rectum pregnancy but it does not appear to be
Contraindications: should not be any more harmful than azathioprine.
indicated for at least 28 days following Tacrolimus and mycophe-nolate mofetil
major surgery; the incision should be are contraindicated in pregnancy by the
fully healed prior to initiation of the manufacturers themselves.
chemotherapy
Side effects: serious and in some case 14.2.1 ANTIPROLIFERATIVE
fatal hemorrhage has occurred with non- IMMUNOSUPPRESSANTS
small cell lung cancer treated with
chemotherapy; gastrointestinal Azathioprine is used widely by the
perforation and impaired wound healing; transplant recipients and to treat a
hypertensive crisis, nephritic syndrome, number of autoimmune diseases, usually
congestive heart failure when corticosteroid therapy alone fails to
Dose: 5mg/kg given once every 14 days provide adequate control. The
as an IV infusion until disease predominant toxic effect is myelosup-
progression is detected pression, although hepatic toxicity is also
very common. In term therapy the blood
Proprietary Preparations counts must be monitored to check the
Avastin(I) (Roche), Inj., 100 mg/4 ml, Tk. myelosuppression. The drug is
56,444.80/4 ml Vial
metabolized to give mercaptopurine, a
Bevastim (Beacon), Inj., 100 mg, Tk. 20,000/Vial
purine analogue that inhibits DNA
529
synthesis. Both cell mediated and

antibody-mediated immune reactions are Indications: prophylaxis of acute renal,
depressed by this drug since it inhibits cardiac or hepatic transplant rejection
clonal proliferation in the induction phase Cautions: blood count every week for 4
of the immune response by a cytotoxic weeks then twice a month for 2 months
action on dividing cells. then every month in the first year elderly
Mycophenolate mofetil has a more patients, risk of haemorrhage, ulceration
selective mode of action than and perforation; delayed graft function;
azthioprine. It is licensed for the susceptibility to skin cancer
prophylaxis of acute rejection in renal Interactions: anion exchange resin
and cardiac transplantation when used in colestyamine reduces absorption;
combination with ciclosporin and antacids reduce absorption of the drug
corticosteroids though the risk of Contraindications: breast-feeding,
opportunistic infection and blood pregnancy (exclude before starting and
disorder such as leucopenia is higher. avoid for 6 weeks after discontinuation)
Cyclophosphamide and chlorambucil Side-effects: gastrointestinal discom-
are less commonly prescribed as forts, hypertension, edema, dyspnoea,
immunosuppressants. cough, rhinitis, dizziness, insomnia,
headache, tremor, infection, leucopenia,
AZATHIOPRINE anaemia, thrombocytopenia, leucocyto-
sis, polycythemia, electrolytes
Indications: transplant recipient and disturbances, hyperglycemia, renal
auto immune diseases damage, haematuria, acne, lympho-
Cautions: monitor blood count weekly proliferative disease
for 4 weeks; thereafter reduce frequency Dose: renal transplantation: by mouth, 1
of monitoring to at least every three g twice daily starting within 72 hours of
months; the doses to be reduced in transplantation or by intravenous
hepatic and renal impairment; elderly infusion, 1 g twice daily within 24 hours
patients and pregnancies of transplantation for up to maximum 14
Interactions: see Appendix-2. days
Contraindication: hypersensitivity to Cardiac transplantation: by mouth 1.5 g
azathioprine or mercaptopurine twice daily within 5 days of
Side-effects: hypersensitivity reactions, transplantation.
dose related bone marrow suppression, Note: Patients should be warned to
nausea hair loss and increased report immediately any signs or
susceptibility to infections and colitis in symptoms of bone marrow suppression
patients also receiving corticosteroids e.g. infection, inexplicable bruising or
Dose: by mouth, by intravenous injection bleeding
over at least 1 minute (followed by 50 ml
sodium chloride intravenous infusion) or Proprietary Preparations
Cellcept(I) (Roche), Tab., 500 mg, Tk.
by intravenous infusion;
141.76/Tab.
Autoimmune conditions: 1-3 mg/kg daily, Mycophenolat-Mofetil (Novartis), Tab., 500
adjusted according to response; mg, Tk. 67.46/Tab.
Suppression of transplant rejection, Mycophenolat-Mofetil sandoz(I) (Sandoz),
initially up to 5 mg/kg then 1-4 mg/kg Tab., 500 mg, Tk. 67.46/Tab.
daily according to response Mycotil (Techno), Tab., 500 mg, Tk.
55.00/Tab.
Myfortic (I) (Novartis), Tab., 180 mg, Tk.
79.00/Tab.; 360 mg, Tk. 157.00/Tab.
G-Azathiopine (Gonoshasthaya),Tab., 50mg,
Phenocept (Renata), Tab., 500 mg , Tk.
Tk. 8.00/Tab.
65.00/Tab.
Imuran(I) (GSK), Tab., 50 mg, Tk.
1,244.64/Tab.
MYCOPHENOLATE MOFETIL
530
14.2.2 CORTICOSTEROIDS AND Basiliximab and daclizumab are

OTHER monoclonal antibodies that prevent T
IMMUNOSUPPRESSANTS lymphocytes proliferation; they have
recently been introduced for prophylaxis
Corticosteroids have great clinical of acute rejection in allergic renal
value in the treatment of acute transplantation. They are given with
lymphoblastic leukemia, malignant ciclosporin and corticosteroid
lymphomas etc. It is also active in immunosuppressant regimens; their use
endocrine cancers. Glucocorticosteroids should be confined to specialist centers.
also serve a function in the treatment of
several frequently occurring side effects BASILIXIMAB
of malignancies as well as general
palliative therapy. The corticosteroids Indications: see notes above
are also powerful immunosuppressants, Side-effects: severe hypersensitivity
that are used to prevent organ transplant reactions and cytokine release syndrome
rejection, and in high dose to treat have been reported. see section 14.1
rejection episodes. Corticosteroids may Cautions: breast feeding and pregnancy
cause osteoporosis, iatrogenic Cushing’s (contraception during treatment and up
syndrome, suppress response to to 16 weeks after last dose)
infection and allow diseases such as Contraindications: known
septicemia or tuberculosis to reach an hypersensitivity to basiliximab or any
advanced stage before being recognized other component of the formulation
(see also section 5.3; 9.1.2; 10.3&12.3) Dose: by intravenous injection or by
Ciclosporin (cyclosporin) is a intravenous infusion,20mg within 2 hours
calcineurin inhibitor, a powerful before transplant surgery and20mg 4
immunosuppressant that is non- days after surgery; withhold second dose
myelotoxic but nephrotoxic. It has ifsevere hypersensitivity or graft loss
relatively selective effects on T occurs; CHILD and ADOLESCENT 1–17
lymphocytes. It can be given orally or by years, body-weight under 35 kg,10mg
IV infusion. Ciclosporin has within 2 hours before transplant surgery
revolutionized the field of organ and and10mg 4 days after surgery; body-
tissue transplantation, significantly weight over 35 kg,adult dose
reducing the morbidity and the incidence
of rejection. It is particularly useful for the Proprietary Preparation
prevention of graft rejection following Simulect(I) (Novartis), Inj.,(I.V infusion) 20
bone marrow and kidney transplantation mg/vial, Tk.102884.00/Vial
and for prophylaxis and treatment of
graft- versus-host disease. Its most CICLOSPORIN
serious toxic effect is on the kidney
which is resulted in increased Indications: as the notes above and
concentration of blood urea and under atopic dermatitis, psoriasis and
creatinine. Hypertension is not so very rheumatoid arthritis
uncommon. Cautions: monitoring of kidney function
Tacrolimus is also a calcineurin is very important. Dose dependent
inhibitor. Although chemically not related increase in serum creatinine and urea
to ciclosporin it has a similar mode of during first few weeks may necessitate
action and side effects with a greater dose reduction in transplant patients or
incidence of neurotoxicity and discontinuation in non-transplant
nephrotoxicity. In some cases patients; liver functions to be monitored
cardiomyopathy is also common. based on serum bilirubin and liver
Disturbances of glucose metabolism also enzymes; monitor blood pressure;
appear to be significant; hypertrichosis discontinue if hypertension develops.
appear to be less of a problem than with Monitor serum potassium especially in
ciclosporin. marked renal impairment; pregnancy
531
and breast feeding. One has to keep in measurements; discontinue after 3

mind about Nephrotic syndrome, atopic months if no improvement in
dermatitis, psoriasis and rheumatoid glomerulonephritis or glumerulosclerosis
arthritis. (after 6 months in membranous
Note: contains polyethoxylated castor oil glomerulonephritis)
which has been associated with
anaphylaxis- observe for at least 30 Proprietary Preparations
minutes after starting infusion and at Imural (Techno), Cap., 100 mg, Tk.
frequent intervals thereafter 60.00/Cap.
Contraindications: uncontrolled hyper- Sandimmun Neoral(I) (R.P. Scherer) Cap., 25
mg, , Tk. 59.00/Cap.; 50 mg, Tk.
tension or infections 117.00/Cap.; 100 mg, Tk. 234.00/Cap.
Interactions: see Appendix-2 Sporium (Incepta), Solu, 10 gm/100 ml, Tk.
Side-effects: commonly dose 2,385/10 gm
dependent increase in serum creatinine
and urea during first few weeks and less TACROLIMUS
commonly renal structural changes on
long term administration; oedema,
pancreatitis, neuropathy, confusion, Indications: used to prevent body from
paresthesia, convulsions, amenorrhea; rejecting a heart, liver, or kidney
muscle weakness, cramps, myopathy, transplant. It may be used along with
gynaeco-mastia; thrombocytopenia, other medicines and see also notes
haemolytic uraemic syndrome; hyper- above
trichosis, tremor, hypertension (specially Cautions: see section 14.1 and notes
in heart transplant patients) hepatic above; monitor blood pressure, ECG,
dysfunction, fatigue, gingival hyper- fasting blood-glucose concentration
trophy, gastrointestinal disturbances, Interactions: see Appendix-2
and burning sensation in hands and feet, Contraindications: pregnancy breast-
hyperkalaemia, hyperuricaemia, hypom- feeding; hypersensitivity to macrolides;
agnesaemia avoid concurrent administration with
Dose: organ transplantation, used alone, ciclosporin
10-15 mg/kg by mouth before 4-12 Side-effects: see section14.1 and
transplantation followed by 10-15 mg/kg notes above
daily for 1-2 weeks postoperatively then Dose: consult product literature
reduced to 2-6 mg/kg daily for
maintenance (dose should be adjusted Proprietary Preparation
Tacrolimus Sandoz (Sandoz), Cap., 1 mg,
by monitoring blood concentrations and Tk. 42.82/Cap.; 5 mg, Tk. 174.80/Cap.
renal function); dose to be lower if given
concomitantly with other
14.2.3 RITUXIMAB
immunosuppressant; if necessary one
third oral dose can be given by
intravenous infusion over 2-6 hours Rituximab is a monoclonal antibody that
Bone marrow transplantation, prevention has recently been introduced for the
and treatment of graft-versus-host treatment of chemotherapy of resistant
disease, 3-5 mg/kg daily by intravenous advanced follicular lymphoma. It causes
infusion over 2-6 hours from day before lysis of B lymphocytes. Rituximab should
transplantation to 2 weeks post be given very carefully in patients with a
operatively (12.5-15 mg/kg daily by history of angina, arrhythmia and heart
mouth) then 12.5 mg/kg daily by mouth failure. Full resuscitation facilities should
for 3-6 months then tailed off ( may take be ready as with other cytotoxic drugs.
up to a year after transplantation) Side-effects include rash, pruritus, fever
Nephrotic syndrome, by mouth, 5 mg/kg and chills, nausea and vomiting,
daily in 2 divided doses; CHILD 6 mg/kg angioedema, bronchospasm and
daily in 2 divided dose according to dyspnoea
proteinuria and serum creatinine
532
An analgesic and antihistamine to be INTERFERON ALFA

given to the patients before each dose of
Rituximab as prophylactic. Indications: AIDS related Kaposis
sarcoma, hairy cell leukemia, follicular
RITUXIMAB lymphoma, chronic myelogenous
leukemia, lymph or liver metastasis of
Indications: chemotherapy resistant carcinoid tumor, chronic hepatitis B,
advanced follicular lymphoma. chronic hepatitis C, adjunct to surgery in
Cautions: see notes above but for full malignant melanoma and maintenance
details consult product literature; of remission in multiple myeloma; see
pregnancy also the notes above
Contraindications: pregnancy and Cautions: consult product literature
breast-feeding Interactions: see also Appendix-2.
Side-effects: see notes above Contraindications: consult product
Dose: 375 mg/m2 administered for once literature.
weekly for 4 weeks (at day 01, day 08, Side-effects: see notes above
day 15, and day 22). In diffuse NHL it Dose : for chronic hepatitis B: Interferon
should be administer along CHOP at day alfa-2a is given in a dose of 2.5 to 5
1 of each chemotherapy. million units/m2 body surface 3 times a
week by SC injection for 4 to 6 months;
Proprietary Preparations For chronic hepatitis C: Interferon alfa-2a
Mabthera(I) (Roche), Inj. 500 mg/50 ml, is given in a dose of 3 to 6 million
Tk.135,406.30/Vial; 100mg/10 ml,Tk. units/m2 body surface 3 times a week for
27,081.13/Vial 4 to 6 months followed by 3 million units
Rituxim(Beacon), Inj., 100 mg, Tk.
13,000.00/Vial ; 500 mg, Tk. 60,000.00/Vial
3 times a week for an additional 6
months
14.2.4 INTERFERONS
Roferon-A(I) (Roche), Inj., 3 MIU, Tk.
The interferons are a family of proteins 2,391.53/Vial; 4.5 MIU, Tk. 3,531.70/Vial
that are produced by cells in response to
viral infections or stimulation with double PEG INTERFERON ALFA
stranded RNA, antigens or mitogens.
They may be produced through Indications: combine with ribavirin for
recombinant DNA technology. The chronic hepatitis C; as monotherapy if
interferons can interfere with subsequent ribavirin not tolerated or contra-indicated
viral challenge, and they have many Interactions: see Appendix-2
immunomodulating and antiproliferative Side-effects: see notes above
effects. Dose: Consult with oncologist
Interferon Alfa: is derived from
leucocytes, macrophages and through Proprietary Preparations
recombinant DNA technology. Interferon Pegasys (I) (Roche), Inj. 180 mcg/ml, Tk. Tk.
alfa preparations are also used in the 25,051.25/Vial; 135 mcg/ml, Tk. Tk.
treatment of chronic hepatitis B and 22,576.23/Vial
chronic hepatitis C, certain lymphomas Peg Intron(I) (Schering), Powder and Solvent
and solid tumors. The symptoms of for solution for inj., 80 mcg/vial, Tk.
side-effects are dose related which 12698.94/0.5 ml Vial
Optipeg-A(Incepta), Inj.,( P.F Syringe), 180
include nausea, influenza like symptoms, mg/ Syringe , Tk. 9,800.00/Syringe ;135
lethargy, myalgia, hypotension and mg/Prefilled Syringe , Tk. 8,800.00/Prefilled
arrhythmia. Severe bronchospasm, Syringe
nephrotoxicity and hepatotoxicity have
been reported.
533
Pegin (Beacon), Inj., 135 mg/ Syringe, Tk. radiation may impair the response of the
8,800.00/Prefilled Syringe ;180 mg/ Syringe, drug
Tk. 9,800.00/ Syringe Side-effects: most common local
reactions are transient dysuria and
14.2.5 ALDESLEUKIN urinary frequency, transient fever, skin
rash, arthralgia, or migratory arthritis,
Aldesleukin is a preparation of systemic BCG reactions
recombinant interleukin-2 has had some Dose: induction treatment comprises 6
action on metastatic renal cell carcinoma weekly intravesical treatment with BCG
unresponsive to other therapy at the Immunotherapeutic, each treatment
expense of profound toxic effects due to dose comprises 3 vials of the BCG
vascular leakage causing pulmonary Immunotherapeutic. After a 6 weeks
oedema and hypotension. Bone marrow, pause, another dose of 3 vials of the
hepatic, renal, thyroid and CNS toxicity BCG Immunotherapeutic should be
are also severe. given intravesically once weekly for 1-3
weeks. 3 weekly doses should definitely
14.2.6 BCG be given to patients who still have
IMMUNOTHERAPEUTICS evidence of bladder cancer.
The drug promotes local acute 14.3. SEX HORMONES AND

inflammatory and subacute HORMONE ANTAGONISTS
granulomatous reactions with histiocytic IN MALIGNANT DISEASES.
and leucocytic infiltration in the
epithelium of the urinary bladder. The 14.3.1 ESTROGENS
local inflammatory effects are associated 14.3.2 PROGESTOGENS
with an elimination or reduction of 14.3.3 ANDROGENS
superficial cancerous lesions of the 14.3.4 HORMONE ANTAGONISTS
urinary bladder. The anti-tumour effect
appears to be T-lymphocytes dependent. Tumours derived from hormone-
sensitive tissues may be hormone-
BCG IMMUNOTHERAPEUTICS dependent. Their growth can be inhibited
by hormones, with opposing actions, by
Indications: for the treatment of hormone antagonists or by agents that
superficial transient cell carcinoma of the inhibit the synthesis of relevant
urinary bladder; for intravesical use in hormones. Hormones and hormone
the treatment and prophylaxis of primary analogues have inhibitory actions on
or recurrent carcinoma in situ of the particular tissue and can play an
urinary bladder important role in the treatment of breast,
Cautions: pregnancy, lactation, prostate, and endometrial cancer. The
pneumonitis, hepatitis, and other organ objective of the hormone therapy is to
dysfunction outside of gastrointestinal provide excellent relief of symptoms for a
tract with granulomatous inflammation period of years. Response to the
on biopsy, respiratory distress treatment and toxicity to be carefully
Contraindications: receiving monitored and treatment to be changed
immunosuppressive therapy (with drugs if progression occurs or side-effects
or radiation) or with compromised exceed benefit.
immune systems because of the danger
of a systemic BCG reaction, pyrexia of 14.3.1 ESTROGENS
unknown origin, urinary tract infection
caused by bacteria Diethylstillbestrol (stillbestrol), a
Interactions: drug combination synthetic non-steroidal estrogen has
containing bone marrow depressants been used in the palliation of prostate
and or immunosuppressants and or and breast cancer. Dose related side-
534
effects include nausea, fluid retention MEDROXYPROGESTERONE

and arterial and venous thrombosis. ACETATE
Impotence and gynecomastia occur in
men and withdrawal bleeding may occur Indications: see notes above
in women. Hypercalcaemia and bone Cautions: diabetes, hypertension,
pain may also occur in breast cancer. cardiac or renal disease
Stillbestrol should be used with caution Contraindications: pregnancy,
in cardiovascular disease, hepatic and undiagnosed vaginal bleeding, hepatic
renal impairment; it is contraindicated in impairment or active liver disease,
pregnancy. severe arterial disease, breast and
Fosfestrol a non-steroidal estrogen has genital tract cancer
become activated to stillbestrol and is Side-effects: acne, urticaria, fluid
used for prostate cancer. Side-effects retention, weight changes, gastrointes-
are as for diethylstilbestrol; in addition, tinal disturbances, changes in libido,
perineal pain may complicate breast discomfort, premenstrual symp-
intravenous use. toms, irregular menstrual cycles; also
Ethynylestradiol is the most potent depressions, insomnia, somnolence,
estrogen available; unlike other alopecia, hirsutism, anaphylactoid
estrogens it is slowly metabolized in the reactions
liver. It is used in breast cancer. Dose: by mouth, endometrial, prostrate
and renal cancer, 100-500 mg daily;
FOSFESTROL TETRA SODIUM breast cancer, various doses in range
0.4-1.5 g daily
Indication: prostrate cancer By deep intramuscular injection into
Caution: see under diethylstilbestrol and gluteal muscle, various doses in range 1
notes above g daily down to 250 g weekly
Side-effects: also nausea and vomiting:
after intravenous injection peritoneal Proprietary Preparations
irritation and pain on bony metastasis see section: 5.4.2.2
Dose: by slow intravenous injection, 0.6-
1.2 g daily for at least 5 days; NORETHISTERONE
maintenance, initially up to 240 mg 3
times daily for 7 days then reducing over Indication: see notes above
14 days to 120-360 mg daily in divided Cautions: see under medroxypro-
doses gesterone acetate
Contraindications: see under
Proprietary Preparation medroxyprogesterone acetate
Honvan (I) (Astamedica) Tab. 50mg,
Side-effects: see under
Tk.20.82/Tab.Inj. 60 mg/ml.
medroxyprogesterone acetate; more
virilizing and greater incidence of liver
14.3.2 PROGESTOGENS
disturbances and jaundice; exacerbation
of epilepsy and migraine
Progestogens are largely used as Dose: breast cancer, 40 mg daily,
second or third line therapy in breast increased to 60 mg daily if required
cancer. They are also used to treat
endometrial cancer and renal cell Proprietary Preparations
carcinoma, but are little used for prostate see section: 5.4.2.2
cancer. Medroxyprogesterone or
megestrol are usually chosen and can
14.3.3 ANDROGENS
be given orally, high-dose or parenteral
treatment cannot be recommended.
Side-effects are mild but may include Testesterone esters are occasionally still
nausea, fluid retention and weight gain. used as second or third line therapy for
metastatic breast cancer.
535
14.3.4 HORMONE ANTAGONISTS exemestane, steroidal aromatase

inhibitors are used to treat advanced
14.3.4.1 BREAST CANCER postmenopausal breast cancer. They are
14.3.4.2 PROSTATE CANCER AND more tolerated than aminoglutethimide
GONADORELIN ANALOGUE and corticosteroid replacement therapy.
Trilostane is also used for post-
menopausal breast cancer. It is well
14.3.4.1 BREAST CANCER
tolerated. Diarrhea and abdominal
discomfort are their main side effects. It
The management of patients with breast may cause adrenal hypofunction and
cancer involves surgery, radiotherapy, need corticosteroid replacement therapy.
drug therapy, or a combination of these. Goserelin, a good gonadorelin analogue
All women with invasive breast cancer is also indicated for advanced breast
should be considered for the adjuvant cancer in post-menopausal women.
therapy, which is determined by
assessment of risk of recurrence,
ANASTROZOLE
estrogen receptor status of primary
tumor and menopausal status.
Tamoxifen is an estrogen antagonist Indications: early breast cancer in
with actions similar to clomiphene. It is postmenopausal women as adjuvant
given in the adjuvant endocrine therapy treatment (treatment following surgery
of early breast cancer and is also given with or without radiation), first-line
for the palliative treatment of advanced treatment for hormone receptor-positive
disease. Tamoxifen is generally well or hormone receptor unknown, locally
tolerated and the most frequent adverse advanced or metastatic breast cancer in
effects are hot flushes, nausea and postmenopausal women.
vomiting. Other adverse effects include Cautions: renal and hepatic impairment
edema, vaginal bleeding, pruritus, Contraindications: pregnancy and
increased tendency to thromboem- breast-feeding, not for premenopausal
bolism. Treatment with tamoxifen delays women
the growth of metastases and increases Side-effects: arthralgia, arthritis, bone
survival; if tolerated it should be fractures, bone pain, rash (including
continued for at least 5 years. Stevens-Johnson syndrome)
Toremifene, is an antiestrogen which Dose: 1 mg tablet taken once a day
has properties similar to tamoxifen is and consult product literature
used for hormone dependent metastatic Proprietary Preparation
breast cancer in post-menopausal Anastrol (Beacon), Tab.,1mg, Tk.500/Tab.
patients. It is given by mouth, 60 mg
daily. EXEMESTANE
Aminoglutethimide act predominantly
by blocking the conversion of androgen Indication: to treat breast cancer in
to estrogens in the peripheral tissues. postmenopausal women. It is often given
Aminoglutethimide is used as second to women whose cancer has progressed
line treatment for prostate cancer. even after taking tamoxifen therapy for
Toxicity may include drowsiness, drug 2 to 3 year, See notes above
fever, and morbiliform eruption; these Cautions: renal and hepatic impairment
side-effects are generally reversible. It Interactions: see Appendix-2
causes induction of hepatic enzymes Contraindications: pregnancy and
and may require modification of doses of breast-feeding
other drugs. Side-effects: see notes above
Anastrozole and Letrozole are Dose: 25 mg daily
inhibitors of aromatase system used in
the treatment of breast cancer. Recently Generic Preparation
introduced Formestane and Tablet 25mg
536
LETROZOLE with subsequent course starting 45 days

later or on day 2 of cycle if menstruation
Indications: advanced breast cancer in occurs
post-menopausal women in whom anti-
estrogen therapy has failed Proprietary Preparations
G-Tamoxifen (Gonoshasthaya), Tab., 10 mg,
Caution: severe renal impairment
TK.6.00/Tab.; 20 mg, Tk.10.00/Tab.
Contraindications: severe hepatic Tamolex (Beacon), Tab., 10 mg, Tk.
impairment, pre-menopausal women 8.00/Tab.; 20 mg, Tk. 16.00/Tab.
Side-effects: hot flushes, gastroin- Tamona (Beximco), Tab., 10 mg, Tk.
testinal disturbances, chest pain, cough, 10.07/Tab.; 20 mg, Tk. 16.07/Tab.
dizziness, fatigue, headache, infection, Tamoxen (General), Tab., 10 mg, Tk.
musculoskeletal pain, peripheral edema, 10.04/Tab.; 20 mg, Tk. 16.06/Tab.
rash, pruritus
Dose: 2.5 mg daily until tumor 14.3.4.2 PROSTATE CANCER AND
progression is evident GONADORELIN
ANALOGUES
Endofree (Incepta), Tab. , 2.5 mg, Tk. Hormonal treatment in metastatic cancer
40.00/Tab. of the prostate is aimed to deplete
Femara(I) (Novartis). Tab. 2.5 mg, Tk. androgen. Analogues of gonadotropin-
375.00/Tab. releasing hormones, such as buserlin,
Femzole (Beximco), Tab. 2.5 mg, Tk.
40.00/Tab.
goserelin, leuprorelin or triptorelin can
Lenor (Eskayef), Tab. 2.5 mg, Tk. 40.00/Tab. under certain circumstances be made
Lerozol (Square), Tab. 2.5 mg, Tk. 40.15/Tab. use of advanced prostate cancer and in
Letrol (Renata), Tab. 2.5 mg, Tk. 40.15/Tab. some cases of advanced breast cancer
Lexel (Beacon), Tab. 2.5 mg, Tk. 40.00/Tab. in pre-menopausal women.
Loreta(Popular), Tab. 2.5 mg, Tk. 40.00/Tab. The standard treatment is bilateral sub-
capsular orchidectomy, which commonly
TAMOXIFEN[ED] results in response lasting 12-18
months. Alternatively, a gonadorelin
Indications: see notes above analogue may be given.
Caution: increased risk of Gonadorelin analogues are expensive
thromboembolic events when used with and require parenteral administration.
cytotoxics, cystic ovarian swelling, pre- Initially these analogues stimulate then
menopausal women, hypercalcaemia in depress lutenising hormone released by
bony metastasis pituitary. During the first 2 weeks of
Contraindications: pregnancy and treatment there is surge of testosterone
breast-feeding secretion associated with progression
Interactions: see Appendix-2 with prostate cancer. In susceptible
Side-effects: hot flushes, vaginal patients this tumor progression may
bleeding or suppression of menstruation cause spinal cord compression, ureteric
in some premenopausal women, vaginal obstruction or increased bone pain.
discharges, pruritus vulvae, gastro- When such problems are anticipated,
intestinal disturbances, headache, orchiectomy or concomitant use of an
alopecia, rashes, uterine fibroids; visual anti-androgen such as cyproterone
disturbances, leucopenia, sometimes acetate or flutamide are suggested; anti
anemia and thrombocytopenia androgen treatment to be started 3 days
Dose: breast cancer, 20 mg daily for at before the gonadorelin analogues and
least 5 years to be continued for 3 weeks.
Anovulatory fertility, 20 mg on day 2, 3, 4 Cautions: Men at risk of tumor flare
and 5 of cycles; if necessary the daily should be monitored closely during the
dose may be increased to 40 mg then 80 metabolic bone disease in women; the
mg for subsequent courses; if cycles injection site should be rotated.
irregular, start initial course on any day,
537
Side-effects: hot flushes, sweating, Interaction: see appendix-2

sexual dysfunction, vaginal dryness or Side-effects: see notes above
bleeding, and gynecomastia or changes Dose: 1 g once daily
in breast size. Sign and symptoms of Note: Consult product literature for dose
prostate and breast cancer may worsen of concurrent prednisone or prednisolone
initially. Other side-effects include
hypersensitivity reactions injection site Proprietary Preparation
reactions, headache, visual disturban- Zytix (Beacon), Tab., 250mg, Tk.26.67/Tab.
ces, dizziness, arthralgia, gastrointes-
tinal disturbances, weight changes, FLUTAMIDE
sleep disorders.
ANTI-ANDROGENS: Cyproterone Indication: advanced prostate cancer
acetate, flutamide, and bicalutamide Cautions: cardiac disease, hepatic
are anti-androgens which can be used to impairment, abdominal pain,
cover the tumor flare which may occur unexplained influenza-like syndromes
after commencing gonadorelin analogue Interactions: see appendix-2
administration. Cyproterone acetate Side-effects: see notes above
and flutamide are also used alone in Dose: 250 mg 3 times daily
patients with metastatic prostate cancer
refractory to gonadorelin analogue Proprietary Preparation
therapy. Bicalutamide is used alone in Proscan (Renata), Tab., 250 mg, Tk. 12/Tab.
patients with locally advanced,
metastatic prostate cancer. 14.3.4.3 SOMATOSTATIN
Abiraterone: It is used in combination ANALOGUES
with prednisone for the treatment of
patients with metastatic castration-
resistant prostate cancer (mCRPC) who Oxtreotide and the
lanreotide,
have received prior chemotherapy
containing docetaxel
recently introduced
analogues of
ABIRATERONE ACETATE
somatostatin,
Indications: see notes above hypothalamic release
Cautions: cardiovascular disease;
control hypertension and correct inhibiting hormone. They
hypokalemia before treatment. Monitor
blood pressure, serum potassium and are indicated for relief of
symptoms of fluid hepatic impairment
retention at least monthly; diabetes;
symptoms carcinoid
hepatic impairment; renal impairment tumors and acromegaly.
538

14: Drugs Used in Malignant Diseases and For Immunosuppression

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14.

MALIGNANT DISEASES AND IMMUNOSUPPRESSION

MALIGNANT DISEASES AND

14: DRUGS USED IN MALIGNANT DISEASES AND FOR IMMUNOSUPPRESSION

14.1. Cytotoxic drugs p.503

14.1 CYTOTOXIC DRUGS advice from the specialist oncologist.

established. Several drugs were threatening complications from

REGARDING DOSAGE REGIMENS

Despite the advances, chemotherapy anticancer drugs such as bone marrow

Nausea and vomiting: is the most Extravasation: or leakage of cytotoxic

As an antidote to methotrexate (usually FILGRASTIM

(more common after intravenous chemotherapy. For further details

oxalophosphorine treatment and haemorrhagic cystitis. Cyclophospha-

noma, ovarian carcinoma, breast cancer. cancer. Skin pigmentation is the

Melphalan is used in the treatment of

Cautions: hepatic and renal impairment Indications: see note above.

of which is markedly increased in intramuscularly to treat the lymphoma’s,

MITOMYCIN because it tends to accumulate at these

Cadribine is an effective but potentially FU is given usually intravenously

absorbed when given orally. It is 100 mg/m2 IV or SC twice a week for 5

(increase toxicity), filgrastim possibly Gemcitabin HEXAL (I) (Ebewe) Inj.,

Etoposide is the semisynthetic Cautions: and notes above; hepatic

prostate cancer and for pancreatic

ALTRETAMINE Temozolomide is structurally related to

Indications: see notes above Indications: see notes above

PAZOPANIB Indications: see notes above

Dose: 50 mg once daily for patient basis and it is better tolerable

Proprietary Preparations: CARBOPLATIN

Docetaxel, though recently been Indications: In combination with

Contraindications: patients with serious Xelpac (Beacon), Inj(I.V Infusion), 100mg/Vial,

Proprietary Preparations TRASTUZUMAB

Generic Preparations TRETINOIN

synthesis. Both cell mediated and

14.2.2 CORTICOSTEROIDS AND Basiliximab and daclizumab are

and breast feeding. One has to keep in measurements; discontinue after 3

An analgesic and antihistamine to be INTERFERON ALFA

The drug promotes local acute 14.3. SEX HORMONES AND

effects include nausea, fluid retention MEDROXYPROGESTERONE

14.3.4 HORMONE ANTAGONISTS exemestane, steroidal aromatase

LETROZOLE with subsequent course starting 45 days

Side-effects: hot flushes, sweating, Interaction: see appendix-2

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