Therapeutic use of carminomycin in Ewing's sarcoma in children]

The therapeutic effect of carminomycin in various combinations with other antitumor drugs, i. e. vincristin, cyclophosphan, dactinomycin and metatrexate was studied in clinics on 18 children with wide-spread Juing sarcoma. Satisfactory direct effect was observed with the use of the above combinations in 47.0 per cent of the patients, which was evident from a decrease in the secondary tumor, disappearance of the pains and improvement of the general state of the patients.     

Use of carminomycin in combination with UHF hyperthermia in the therapy of sarcoma 180]

It was found that combined treatment of sarcoma 180 with local U. H. F.-hyperthermia and carminomycin resulted in the tumor growth inhibition by more than 90 per cent, which was much higher than the effect of every agent alone. The thermochemotherapy allowed a decrease in the dose of the antibiotic without decreasing the antitumor effect. The U. H. F.-hyperthermia has an independent tumorolytic effect and promotes selective accumulation of carminomycin by the tumor.     

Treatment results in osteogenic sarcoma in children and adolescents with the use of karminomycin

Carminomycin, a new antibiotic made in the USSR, was used in the treatment of 21 patients aged 5 to 15 years with extended osteogenic sarcoma. As a result of the treatment the number of the patients with lifetime prolonged for 1-2 years increased from 7.6 to 46 per cent. It was shown that the drug might be used for the prophylaxis of the localized forms of the disease in children.     

Use of carminomycin on adult patients with acute leukemias]

The data on the clinical trials of karminomycin, a new antitumor antibiotic are presented. The drug was used in the treatment of 46 adult patients with leukemia. Karminomycin was used in primary inducing therapy and treatment of relapses. The results of the trials showed that karminomycin had a definite therapeutic activity in treatment of acute myeloblast leukemia at various stages of the process. A rapid effect of the antibiotic provided its use in emergency cases with rapidly progressing variants of the disease.     

Immunotherapy of osteogenic sarcoma with transfer factor

Summary Fifteen patients with osteogenic sarcoma were treated with transfer factor derived from leukocytes of their household contacts. Eight of the fifteen patients were tumor-bearing, and transfer factor therapy was correlated with increased cell-mediated immunity in peripheral blood lymphocytes and with lymphocytic infiltrates into the tumors. There was no marked increased in survival time as compared with historical controls, but this therapy did not accelerate the disease, and there were no untoward side effects.Seven of the fifteen patients were disease-free when transfer therapy was initiated shortly after surgical removal of the primary tumor (five patients) or solitary pulmonary metastases (two patients). These patients received transfer factor injections every 2 weeks for 1–2 years. Six of the seven patients are disease-free 62–82 months after surgery. Compared with probabilities of 5-year survival computed from historical controls, this is significant at P<0.008. Abbreviations used in this paper are: CI, cytotoxicity index; GCT, giant cell tumor of bone; HHC, household contacts; HHC_os, household contacts of patients with osteogenic sarcoma; MIC, mononuclear inflammatory cell; TFCI, transfer factor cytotoxicity index; TSTF, tumor-specific transfer factor.     

Experience with using carminomycin in oncological clinical practice]

Carminomycin is an original antitumor antibiotic from the anthracycline group isolated at the Institute of New Antibiotics (USSR) in 1973. Pharmacological investigation of carminomycin revealed its satisfactory absorption from the gastrointestinal tract which proved to be a distinguishing property of the antibiotic as compared to other anthracyclines such as adriamycin and rubomycin. The clinical trials of carminomycin showed that it was mainly active against soft tissue sarcoma and breast cancer, lymphosarcoma, neuroblastoma, Wilms' tumor and Ewing's sarcoma in children, as well as acute leukemia. Various regimens for the antibiotic administration were applied: short-term, single and long-term. Suppression of hemopoiesis was considered as a limiting toxic effect. By the data available carminomycin had lower cardiotoxicity as compared with rubomycin and adriamycin. Development of oral carminomycin is believed promising.     

Immunodepressive action of carminomycin and rubomycin derivatives]

The immunodepressive effects of carminomycin and its 3 semi-synthetic derivatives, as well as rubomycin and its derivative R-103 were compared. It was found that 14-hydroxycarminomycin was much superior to the other substances in the experiments with synthesis induction suppression of antibodies against sheep red cells in mice. Suppression of the rejection of the skin allogenic grafts in the mice by carminomycin was higher as compared to that by the other substances. Probably different populations of the immune competent cells have selective sensitivity to separate anthracyclines.     

Possibilities of preventing cardiotoxic complications in chemotherapy with carminomycin]

Carminomycin chemotherapy of the patients with malignant tumors is often complicated with cardiopathy which is sometimes assymptomic and registered only electrocardiographycally. Chemotherapy on the background of reparative regeneration stimulators from the series of synthetic pyrrimidine derivatives, such as methyluracyl for oral use and a soluble salt of methyluracyl for parenteral administration significantly decreased the rate of the cardiotoxic complications and promoted a decrease in their level. The use of methyluracyl and its soluble salt did not decrease the therapeutic effect of carminomycin. Methyluracyl and its soluble salt may be recommended for prophylaxis of cardiotoxic complications in chemotherapy of malignant tumors with carminomycin.     

Toxicity and pharmacological properties of carminomycin complex components]

Acute toxicity of the components of the carminomycin complex after intravenous administration to albino mice increased as follows. I less than II less than III. Component II induced a decrease in all the indices of the bone marrow and peripheral blood of the animals. It was most pronounced in dogs. The dogs died after administration of component II in the lethal doses as a result of the bone marrow aplasia. The indices of the functional state of the liver and kidneys in the animals after administration of components I and II changed slightly. Component III administered repeatedly to rabbits even in low doses induced significant impairments in the function of the liver and kidneys. Component II differed from component I by more pronounced cardiotoxicity. On the basis of the experimental data and the results published earlier component I is recommended for clinical trials as the least toxic one.     

Serum enzymatic activity in oncological patients treated with carminomycin]

Karminomycin effect on the activity of some serum enzymes, such as hexokinase (HK), lactate dehydrogenase (LDG), its isoenzymes and glucose-6-phosphatase (G-6-P-ase) was studied. Biochemical assays were applied to 52 patients with neglected malignant tumors. The course dose of the drug was on the average 72mg. The objective antitumor effect was registered in 15 patients. A reliable increase in the values of LDG-5 and G-6-P-ase was observed after the treatment course in the combined group consisting of all the patients subjected to the biochemical assay. Normalization of the serum enzyme spectrum was observed in 15 patients effectively treated with karminomycin: activity of HK and the cathode fractions of LDG decreased. When treatment with karminomycin was ineffective (37 cases), the changes in the enzymatic activity recorded before the treatment further aggraviated. It was found that the level of G-6-P-ase in the patients' treated with karminomycin increased independent of the treatment effect which was probably associated with its toxic effect on the liver. The increase was reversible.     

Antitumor activity of carminomycin antibiotic used orally]

Antitumor activity of karminomycin used perorally was studied with respect to 3 strains of mouse transplantable tumors, i. e. one ascitic strain of lymphadenosis NK/LI and two solid strains of lymphosarcoma L10-1 and sarcoma 180. Karminomycin was shown to have a high antitumor activity against the above tumors on its oral administration. In the experiments with lymphadenosis NK/LI the efficiency of karminomycin was higher when it was used perorally as compared to its intravenous administration. It was found that karminomycin had practically the same inhibitory effect on growth of lymphosarcoma L10-1 and sarcoma 180 on its peroral and intravenous administration in doses equivalent by their toxicity.     

Antiviral action of carminomycin and some of its derivatives]

Carminomycin was shown to inhibit the development of both the DNA-containing variolovaccine virus and the RNA-containing grippe virus in chick embryos. Comparison of the effects of rubomycin, carminomycin, 14-oxy-carminomycin and carminomycin complex with bovine serum albumin in experiments with chick embryos showed that the inhibitory effect of carminomycin and its derivatives on the development of the grippe virus was much higher than that of rubomycin. The carminomycin derivatives proved to be much more active in this respect than the initial antibiotic. Carminomycin and its derivatives had a therapeutic effect on mice with experimental grippe pneumonia also on their oral use.     

Mechanism of the myeloinhibitory effect of carminomycin]

The proliferative activity and level of aberrant mitoses in the cells of the bone marrow were studied experimentally on 223 noninbred mice treated with carminomycin administered intraperitoneally in single (LD50) and repeated doses. When the antibiotic was used in a single dose the values of the mitotic activity of the bone marrow elements did not correspond to the severity of depression and thir quantitative composition, which was explained by an impairement of the mitosis quality and possible interkinetic destruction of a significant part of both erythroid and immature myeloid cells capable of division at early stages after the exposure. At the same time the level of the bone marrow devastation under conditions of the treatment with repeated doses was mainly determined by inhibition of the erythronormoblast proliferative activity.     

Effect of carminomycin on the immunological reactivity of the body]

The morpho-functional state of the muscle lymphoid tissue of mice treated with karmionmycin (LD50, 1.1 mg/kg) was studied experimentally. Development of a number of changes evident of the cell disorganization in the lymphoid tissue was shown. The cytological shifts in the thymus and spleen were reversible, while the destructive period in the strumous gland was more prolonged. The morpho-structural normalization of the spleen did not coincide with reduction of its immunological function. The studies on the karminomycin effect on the kinetics of the primary immune response showed dependence of the antibiotic effect on the temporal ratio between the antigenic stimulus and the drug administration. The antibiotic had no effect on the inductive phase of the primary immune response but significantly suppressed its productive phase. On reproduction of the secondary immune response, a decrease in the content of the antibody-forming cells in the spleen was observed, production of the circulating antibodies remaining unchanged.     

Blood coagulation system in oncological patients treated with rubomycin, adriamycin and carminomycin]

Systems of blood coagulation in patients treated with antibiotics of the anthracycline group were studied. Rubomycin was used in the treatment of patients with acute leukemia Adriamycin and carminomycin were used in the treatment of patients with solid tumors. The antibiotics affected the process of blood coagulation mainly through their cytostatic effect on thrombocytopoesis. Thrombocytopenia induced deficit of thrombocytal factors participating in the process of blood coagulation which resulted in hypocoagulation and hemorrhagic complications. The plasmic factors did not significantly change during the antibiotic therapy. A tendency to decrease in the levels of prothrombine, fibrinase and fibrinogen was noted which was possible due to an inhibitory effect of the antibiotics on the function of the reticuloendothelial tissue cells or indirectly to suppression of the tumor process. More pronounced changes in the system of blood coagulation of patients treated with rubomycin were probably associated with inferiority of the thrombocytal apparatus of the patients with acute leukemia treated with the antibiotic.