RU2200008C1 - Method for treating the cases of generalized tumor development processes - Google Patents

Abstract

FIELD: medicine. SUBSTANCE: method involves intravenously or subcutaneously administering preliminarily prepared cytostatic agent and leukostimulator agent mixture. 5-fluoruracyl is usable as cytostatic and sodium salt of DNA is usable as leukostimulator agent. Derinate is usable as the sodium salt of DNA. EFFECT: enhanced effectiveness of treatment. 2 cl

Description

 The invention relates to medicine, namely to oncology, and can be used in the treatment of cancer of various localizations at the stage of generalization with metastation to the liver, lungs, bones, lymph nodes, with resistance to chemotherapy or the inability to carry it out due to persistent leukopenia or severe general condition.

 There is a method of treating generalized tumor processes when chemotherapy is not possible in its pure form using the sodium salt of native deoxyribonucleic acid (DNA). (See patent application of the Russian Federation 93002773, "A method for the treatment of hematopoiesis disorders", 1993).

 However, this method can only be considered as maintenance therapy.

 There is a method of treating generalized tumor processes by administering an anthracycline series of antitumor antibiotics in combination with the sodium salt of native DNA (see RF patent 2007165, "Method for the treatment of malignant neoplasms", 1993). In this method, a complex of drugs is administered intramuscularly, but when administered intramuscularly or subcutaneously, it can cause necrobiotic processes at the injection site (up to 30% of cases).

 A known method of treating generalized tumor processes by introducing a complex of anthracycline antibiotic and sodium salt of DNA with the preliminary creation of a conjugate with blood proteins. At the same time, the necrobiotic effect at the injection site of the complex is reduced (up to 5% of cases), the transportation of the antitumor drug from the depot to the tumor cells occurs in a form inactive for healthy tissues (see RF patent 2155590 "Method for the treatment of generalized tumor processes", declared June 20, 1996 published on September 10, 2000).

 However, the known complex does not have the necessary selectivity for the cells of generalized tumors of gastric cancer and colon cancer. Perhaps the development of resistance to anthracycline antibiotics.

 There is a method of treating cancer by sequential intravenous administration of leucovorin and 5-fluorouracil in order to increase the effective time of exposure of the drug to the tumor. Leucovorin is used as a biochemical modulator of fluorine derivatives of pyrimidine (see Chemotherapy of Tumor Diseases. Quick Guide. Edited by N.I. Translatorova. Moscow, 2000, p. 82, 121). The treatment method selected for the prototype.

 However, the main disadvantage of 5-fluorouracil is manifested - the impossibility of intramuscular administration due to necrobiosis and a short time of activity in the patient's blood plasma. At the stage of chemiotepapia with prolonged infusions, more than half of patients have complications after treatment in the form of neutropenia or hematopoiesis depression. With common tumor processes, and more than 60% of the number of initially identified patients, when pronounced symptoms of intestinal obstruction, stenosis or compression of the vital organs prevail by the tumor, the effectiveness and toxicity of intravenous infusion of 5-fluorouracil increase, exacerbating the severity of the patient's condition.

 The main objective in the treatment of generalized tumor processes is to increase cell selectivity, increase the contact time of 5-fluorouracil (cytostatic) with the target cell with minimal exposure to healthy tissues and simplifying the method of administration of cytostatic.

 The aim of the present invention is to change the transportation of 5-fluorouracil selectively acting on tumor cells of the gastrointestinal tract, maintaining the concentration of cytostatic in the tumor tissue.

 This goal is achieved by intramuscular or subcutaneous administration of a pre-prepared mixture of a cytostatic agent and a leukostimulator in a state inactive for healthy tissues, with 5-fluorouracil being used as a cytostatic agent and the sodium salt of DNA as a leukostimulator.

 The introduction of a subcutaneously or intramuscularly pre-prepared mixture consisting of 5-fluorouracil and sodium salt of DNA allows you to use the most convenient form of introducing the inactive cytostatic into the muscle, neutralizing the local necrobiotic effect of 5-fluorouracil.

 A mixture consisting of both a cytostatic and a leukostimulator simultaneously prevents cytopenic complications during treatment.

 Observations of patients showed that this approach is comparable in therapeutic effect with the recognized "standard" combination of 5-fluorouracil and leucovorin.

 Specific examples of the use of the invention.

 1. Patient Ch., Born in 1937, diagnosed with colon cancer of 5 cm T3-4NxMx with germination in the wall of the bladder and prostate gland. It was first examined by a proctologist in August 2000.

 Histologically - moderately differentiated cancer. The situation is regarded as inoperable. The selected treatment plan is radiation therapy against the background of intravenous administration of 5-fluorouracil.

 During the period from September to January, the patient received in 2 stages the total dose of radiation therapy 48 Gray and 5-fluorouracil 2 g. During the treatment, a complication arose - acute purulent paraproctitis with moderate leukopenia, requiring surgical opening. NMR of the pelvic organs after the completion of the full stage of radiation therapy revealed the tumor volume unchanged, germination into the wall of the bladder is not excluded.

 Clinically, an inoperable tumor due to the immobility of the walls of the rectum and the infiltration of surrounding tissues.

 From January 15 to March 15, 2001, the patient began to receive chemotherapy according to the proposed method in the form of an intramuscular mixture of 5-fluorouracil with derinate to a total dose of 4.0 g of fluorouracil. The treatment was satisfactory - without complications, the patient was able to work throughout the treatment period. From April 15, 2001, the patient continued treatment in the form of a second course of chemotherapy according to the proposed method - by the time of the start of the course of treatment of subjective conditions about the presence of a tumor, the patient did not note, urination was completely restored, there were no dysuric disorders, regular stool without mucus and blood.

 Repeated NMR of the pelvic organs revealed cancer of the rectum 2-3 cm, a small adenoma of the prostate gland, postradiation cystitis. Clinically, the situation is operable - the planned operational day is June 27, 2001. Assessment of the state of tolerance of the course according to Karnovsky - 1 degree.

 2. Patient D., born in 1953 - after examination by a surgeon at the place of work and proctologist, X-ray colon cancer T3N1M1 (a single metastatic lesion in the left lobe of the liver) was clinically X-ray revealed.

 In October 1999, a conditionally radical operation was a resection of sigma and the left lobe of the liver with a metastatic focus. Histology: Mature adenocarcinoma with an invasion of fiber.

 In November 1999, 1 course of preventive chemotherapy was prescribed with 5-fluorouracil and leucovorin in a total dose of 5-fluorouracil 4 g. Against the background of treatment complicated by herpes, hemorrhagic dermatitis, stomatitis, agranulocytosis of up to 1800 leukocytes, a secondary lesion was identified in the right lobe of the liver 3-3 cm .

 From January 2000 to June 2000, 3 courses of chemotherapy were carried out according to the proposed method with the introduction of 5-fluorouracil intramuscularly, prolongation in a total dose of 4 g each.

 Over the entire period of observation since January 2000 for 1.5 years - the state is stable, without subjective complaints. Ultrasound - stabilization, according to blood biochemistry, studies of indicators of tumor markers of immunograms - a stable condition without pathological changes.

 During treatment, the patient regained her weight (by 10-15 kg), the entire treatment period was able to work. Karnovsky criterion - 1.

 3. Patient P., born in 1930 In the OOD of Yekaterinburg on November 16, 2000, palliative hemicolectosmia for cecum cancer pT4N3Ml, a metastatic process in the liver, was performed. Histologically, adenocarcinoma.

 Palliative chemotherapy with 5-fluorouracil in a dose of 4 g led to complications in the form of anemia of 85 g / l and leukopenia 2500, stomatitis and diarrhea.

 When leukocytes were restored to 3000, the patient continued treatment according to the proposed method with weekly intramuscular injection of a mixture of 5-fluorouracil and sodium salt of DNA in doses of 500 mg and 75 mg, respectively.

 In total, during the period of treatment of the patient from February 1 to June 2001, 2 courses of chemotherapy were carried out according to the proposed technique. When the control ultrasound of the liver after 6 months from the start of treatment - the absence of focal metastatic changes. During this period, the patient gained weight 8-10 kg.

 Assessment by WHO criteria - complete remission. Karnovsky criterion - 1.

 In total, for the period 1999-2000, treatment was performed with inoperable or generalized tumors of cancer of the rectum and colon, stomach, metastatic liver damage in breast cancer, neurosarcoma - 18 patients, including 6 women and 12 men. The age of patients was 45-72 years. When assessing the condition according to WHO criteria, an objective effect was observed in 12 (66%) patients, of which complete remission was observed in 2 (11%). Unstable stabilization up to 3 months or lack of effect in 6 (33%) patients.

Claims (2)

 1. A method of treating generalized tumor processes by administering a complex based on fluoropyrimidine cytostatics, characterized in that a previously prepared mixture of a cytostatic and a leukostimulant is administered intramuscularly or subcutaneously, with 5-fluorouracil being used as a cytostatic and a sodium salt of DNA as a leukostimulator.  2. The method according to p. 1, characterized in that as the sodium salt of DNA using Derinat.