carubicin and Breast-Neoplasms

Topics: Aclarubicin; Anthraquinones; Antibiotics, Antineoplastic; Breast Neoplasms; Carubicin; Cell Survival; Daunorubicin; Doxorubicin; Drug Evaluation; Epirubicin; Heart; Humans; Idarubicin; Leukemia; Menogaril; Mitoxantrone; Naphthacenes; Nogalamycin; Sarcoma; Structure-Activity Relationship

Topics: Aclarubicin; Animals; Antibiotics, Antineoplastic; Breast Neoplasms; Carubicin; Daunorubicin; Doxorubicin; Female; Glycosides; Hodgkin Disease; Humans; Leukemia; Lung Neoplasms; Lymphoma; Naphthacenes; Ovarian Neoplasms; Sarcoma

KRN8602 (3'-deamino-3'-morpholino-13-deoxo-10-hydroxycarminomycin hydrochloride, MX2 x HCl) is a newly developed anthracycline that has been found to be effective against multidrug-resistant tumor cells in vitro and in vivo. In order to clinically confirm these promising preclinical observations, we performed a phase II trial of KRN8602 in patients with anthracycline-resistant metastatic breast cancer.. Of 41 patients registered with metastatic breast cancer, 37 were eligible and were given at least two cycles of KRN8602 15 mg/m2 per day at 3-4 week intervals by intravenous bolus injection on days 1, 2, and 3.. Of the 37 patients, 6 (16.2%, with a 95% confidence interval of 4.3-28.1%) had a partial response (PR). No complete responses (CRs) were observed. The difference between response rates according to prior history of anthracycline administration was not significant. Myelosuppression was moderately severe, with grade 3 or 4 leukopenia occurring in 65%. Severe nausea/vomiting was observed in 44% of the patients.. The results indicate that KRN8602 has modest activity in refractory metastatic breast cancer and is associated with relatively severe toxicity. Furthermore, the preclinical finding that KRN8602 overcomes anthracycline resistance was not reliably reproduced in this clinical phase II trial.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Breast Neoplasms; Carubicin; Drug Resistance, Neoplasm; Female; Humans; Middle Aged; Neoplasm Metastasis

We performed a preliminary phase II clinical trial of MX2; 3'-deamino-3'-morpholino-13-deoxy-10-hydroxycarminomycin (KRN8602) in patients with metastatic breast cancer who had failed to respond to previous chemotherapeutic regimens after clinical evidence of systemic disease. Twelve patients at a single institute received KRN8602 at a dose of 35 mg/m2 intravenously once every three weeks. All the patients were followed-up until their disease progressed. There was one complete response lasting 17 weeks and one partial response lasting eight weeks. Among the 12 patients, World Health Organization (WHO) grades 3 and 4 neutropenia were observed in five and two patients, respectively. Grade 3 anemia was observed in three patients but severe thrombocytopenia was not observed. Grade 3 nausea/vomiting was observed in eight patients. Alopecia was not observed. The results of this preliminary phase II trial suggest a need for further testing of the anti-tumor activity of KRN8602 in patients with metastatic breast cancer.

Topics: Antibiotics, Antineoplastic; Breast Neoplasms; Carubicin; Female; Humans; Middle Aged

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.

Topics: Adult; Breast Neoplasms; Carubicin; Child; Female; Humans; Kidney Neoplasms; Leukemia, Myeloid, Acute; Liver Neoplasms; Neoplasms; Sarcoma; Soft Tissue Neoplasms; Uterine Neoplasms; Wilms Tumor

Sixty-four patients with advanced progressive breast cancer resistant to conventional treatments were entered into the present study. They were randomized to receive either Carminomycin (CMM) 20 mg/m2 or Doxorubicin (DOX) 75 mg/m2, both drugs being administered by i.v. bolus every 3 weeks until progression of the disease. Five patients were not eligible and response could not be evaluated in another eight patients. Three patients had only one course due to disease-related early death. Among twenty-seven evaluable patients who received at least two courses of DOX one complete response and seven partial responses were observed for an overall response rate of 30%. CMM showed significantly lower (P = 0.04) antitumor activity with only one partial response (4%) among the 24 patients who received at least two courses of therapy. Median duration of response dating from the start of chemotherapy was 46 weeks on DOX (range 18-102+) and 30 weeks for the single partial response on CMM. Although the median time to progression for all patients receiving CMM (9 weeks) was significantly shorter (P = 0.04) than for those receiving DOX (30 weeks), patients on DOX had only a marginally longer duration of survival (P = .28) than those initially treated with CMM. Myelotoxicity was more severe in the CMM treated group than in the DOX group. Other toxicities such as alopecia, nausea and vomiting were slightly more severe in the DOX treated group. On the basis of this and other similar randomized studies, CMM cannot be recommended for further application in the treatment of advanced breast cancer.

Topics: Adult; Aged; Breast Neoplasms; Carubicin; Daunorubicin; Doxorubicin; Drug Evaluation; Female; Humans; Leukocyte Count; Middle Aged; Platelet Count; Random Allocation

Sixty-three evaluable patients with advanced breast cancer were randomly allocated to receive three-week intravenous courses of carminomycin (18 mg/m2) or 4'-epidoxorubicin (90 mg/m2). The former yielded one (3%) partial response for nine weeks among 29 patients whereas, in the other arm, nine (27%) of 34 patients achieved partial response for a median of 28 weeks (range, nine to 36 weeks; p less than 0.02). The major toxic effect of these anthracyclines was leukopenia with median white blood cell nadirs of 1,600/microL (range, 300-4,000/microL) versus 1,800/microL (range, 500-4,300/microL), respectively. Acute nonhematologic toxic effects were qualitatively similar but carminomycin produced significantly less gastrointestinal intolerance and alopecia. Patients whose disease failed to respond to first-line anthracycline received doxorubicin (60 mg/m2) every three weeks. Four partial responses were obtained among 19 patients previously treated with carminomycin. Following 4'-epidoxorubicin therapy, one of 12 evaluable patients also attained partial response. Survival curves were not affected by the initial treatment option. Carminomycin has marginal activity against breast cancer whereas 4'-epidoxorubicin deserves further evaluation of its therapeutic index relative to doxorubicin. The design used in this trial appears attractive for prompt phase II evaluation of anthracycline analogs.

Topics: Adult; Aged; Alopecia; Breast Neoplasms; Carubicin; Daunorubicin; Doxorubicin; Drug Evaluation; Epirubicin; Female; Follow-Up Studies; Heart Diseases; Humans; Leukopenia; Middle Aged; Nausea; Neoplasm Metastasis; Random Allocation; Vomiting

A more than 50% regression of tumor was observed in 19% of 64 patients treated with carminomycin for advanced primary breast cancer, its recurrences and metastases. A clinically-significant effect of treatment was recorded in 42%, while tumor process was arrested for at least 3-4 months in 37% of cases. The index of more than 50% regression of tumor rose to 28% in a group of 27 patients, following repeated courses of the drug. Only a slight toxic side--effect was observed, repeated courses included. Moderate leukopenia and a slight cardiotoxic effect were registered in 17%; phlebitis--in 12%. Carminomycin treatment should be recommended for advanced primary breast cancer, its recurrences an metastases, when other chemotherapeutic means fail to stop tumor process.

Topics: Adult; Aged; Breast Neoplasms; Carubicin; Clinical Trials as Topic; Daunorubicin; Female; Humans; Injections, Intravenous; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Time Factors

A controlled study with two independent cytostatic combinations in advanced breast cancer was performed in total 236 patients. Results of the treatment in 218 evaluable patients are reported. The first combination included cyclophosphamide, methotrexate, 5-fluorouracil, and vincristine (CMFV, 108 patients), the second one carminomycin and dibromodulcitol (CD, 110 patients), both treatments having been administered intermittently. Those patients who became resistant to the first applied schedule or those after five CD cycles, were crossed over to the alternative schedule. Patients were perspectively stratified according to dominant sites of metastases and randomized then to the treatment schedule. Overall response (CR + PR + MR) was achieved in CMFV combination in 35/108 patients (32%), conventional response (CR + PR) in 31/108 patients (29%), complete response (CRP) in 7/108 patients (7%). In CD combination the corresponding values were 34/110 (31%), 27/110 (25%), 1/100 (1%). Response (CR + PR) in patients crossed over from CMFV to CD was seen in 2/37 patients (5%), and from CD to CMFV in 4/36 patients (11%). Median duration of response observed in the CMFV combination was 5.5 months (range 1-12 + months), in the CD combination 4.5 months (range 1-15 months). Toxic reactions were reversible, grade 3 and 4 cardiotoxicity in the CD combination in 4% of patients in the primary treatment and in 14% in patients when crossed over from the primary treatment and in 14% in patients when crossed over from the primary CMFV regimen.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carubicin; Clinical Trials as Topic; Cyclophosphamide; Daunorubicin; Drug Therapy, Combination; Female; Fluorouracil; Humans; Methotrexate; Middle Aged; Mitolactol; Vincristine

Karminomycin was used for the treatment of cases with disseminated cancer of the mammary gland in doses of 5 mg/m2 of the body surface intravenously every day for 5 days (15 patients) or 6 mg/m2 twice a week for 2-3 weeks (30 patients). Partial remission or diminution of the tumor size at least by 50 per cent was observed in 26 and 17 per cent of the patients respectively. The remission duration was from 2 to 6 months. With the use of the shortperiod scheme the frequency of the direct side reactions increased. Leucopenia as a side effect was registered in 100 and 40 per cent of the patients and thrombocytopenia was registered in 18 and 3 per cent of the cases respectively.

Topics: Antibiotics, Antineoplastic; Breast Neoplasms; Carubicin; Clinical Trials as Topic; Drug Evaluation; Female; Humans; Leukopenia; Middle Aged; Time Factors

The new hydrophilic derivatives of 14-hydroxycarminomycin were obtained using 13-dimethyl ketal of 14-bromocarminomycin (6) as the starting compound. The reductive alkylation of 6 with melibiose or D-galactose followed by hydrolysis of the corresponding intermediate bromoketals 9 and 11 produced 3'-N-[-alpha-D-(galactopyranosyl-(1 --> 6)-O-D-1-desoxyglucit-1-yl]-14-hydroxycarminomycin (10) and 3'-N-(1-desoxy-D-galactit-1-yl)-14-hydroxycarminomycin (12), respectively. These novel derivatives 10 and 12 were less toxic than carminomycin or 14-hydroxycarminomycin for leukemia (K562) and breast carcinoma (MCF-7) cells. Importantly, carminomycin, 14-hydroxycarminomycin and compounds 10 and 12 were similarly active for wild type cells and their multidrug resistant (MDR) sublines, K562i/S9 and MCF-7Dox.

Topics: Antibiotics, Antineoplastic; ATP Binding Cassette Transporter, Subfamily B; Breast Neoplasms; Carubicin; Cell Survival; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Female; Genes, MDR; Humans; Leukemia; Structure-Activity Relationship; Tumor Cells, Cultured

The pharmacokinetic properties of KRN 8602, an anthracycline compound, was studied by HPLC following intravenous administration of KRN 8602 to cancer patients. The results were as follows. (1) The plasma concentration-time curve declined as a triphasic function (alpha, beta, gamma) (t1/2 (alpha) = 0.02910, +/- 0.0054 hr, t1/2 (beta) = 0.704 +/- 0.319 hr, t1/2 (gamma) 8.37 +/- 1.37 hr). The blood cell concentration was higher than that in plasma. (2) The distribution volumes of the tissue compartment were larger than those of the central compartment. This result suggested that KRN 8602 would be easily transferred into the tissues. (3) The area under the curve (AUC) of KRN 8602 increased in proportion to the increase of dosage. (4) The metabolites of KRN 8602 were detected in plasma, blood cell and urine. (5) Urinary excretion of KRN 8602 and its metabolites were extremely low.

Topics: Adult; Antibiotics, Antineoplastic; Breast Neoplasms; Carubicin; Drug Evaluation; Female; Humans; Infusions, Intravenous; Middle Aged

The antitumor activity and pharmacokinetics of (7R, 8S, 10S)-10-((3-deamino- 3-(4-morpholino)-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy)-8- ethyl- 7,8,9,10-tetrahydro-1,6,7,8,11-pentahydroxy-5,12-naphthacenedione hydrochloride (KRN8602) were evaluated using five human breast carcinoma xenografts in nude mice. The maximum non-toxic dose of KRN8602 was 2 mg/kg by q4d x 3 intraperitoneal and peroral administration. KRN8602 showed significant antitumor activity against MX-1, which is less sensitive to adriamycin, with the chemotherapeutic indices of 13.0 for po administration and 9.5 for ip injection. Although KRN8602 also inhibited the growth of T-61 significantly, the antitumor activity of this agent against the other three breast carcinoma xenografts was limited. To elucidate this discrepancy, pharmacokinetic analysis and MTT assay were conducted using the KRN8602-sensitive MX-1 and KRN8602-insensitive R-27. While no differences were observed in the area under the curve and the peak concentration of KRN8602 for each tumor, a difference in the sensitivity of the tumor strains was obvious in MTT assay. The efficacy of this agent seemed to depend on the sensitivity of each type of tumor cell rather than the concentration of agent in tumor tissues. If it were possible to select patients with sensitive tumor cells to this agent by the MTT assay, the phase II trial might be completed within a short period by reducing the number of studied patients.

Topics: Animals; Antibiotics, Antineoplastic; Breast Neoplasms; Carubicin; Daunorubicin; Drug Administration Schedule; Drug Screening Assays, Antitumor; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Specific Pathogen-Free Organisms

KRN 8602 is a new antineoplastic drug with the chemical structure, 3'-deamino-3'-morpholino-13-deoxo-10-hydroxycarminomycin hydrochloride. This drug was developed in an attempt to improve the clinical efficacy of currently used anthracyclines. In preclinical studies, KRN 8602 has been shown to produce less cardiotoxicity and alopecia, yet has comparable antitumor effects to adriamycin. In addition, KRN 8602 has shown antitumor effects on adriamycin-resistant tumors. A phase I clinical study was undertaken to determine the toxicity of KRN 8602 given as a single i.v. dose. Toxicity evaluation included CBC with differentials, platelet counts, SMA chemistry profile, EKG, urinalysis, plain chest X-ray and physical examination. Myelosuppression was the major side effect noted with leukopenia, and especially neutropenia, being dose-limiting. The degree of WBC suppression was dose-related and MTD appears to be 30 mg/m2. Nausea and vomiting were observed in cases who had received more than 10 mg/m2. No patient had alopecia. No obvious cardiotoxicity in this study. Maximum total cumulative dose of KRN 8602 was 450 mg/m2. Further observation is necessary to confirm this point. In this study of 10 cases, one breast carcinoma with bilateral lung metastasis revealed definite regression of metastasis for more than 18 months with this agent alone. This patient had previous chemo- and hormone therapy, containing adriamycin. The above preliminary phase I clinical study suggests strongly the usefulness of KRN 8602, and further investigations are indicated.

Topics: Adult; Antibiotics, Antineoplastic; Breast Neoplasms; Carubicin; Daunorubicin; Drug Evaluation; Female; Humans; Injections, Intravenous; Leukopenia; Male; Middle Aged; Nausea; Stomach Neoplasms; Vomiting

Phase I clinical trial of a new semi-synthetic morpholino anthracycline derivative, KRN8602, was performed. Sixteen patients with advanced malignant neoplasms refractory to standard chemotherapies received 27 courses at doses ranging from 1.5 mg/m2/day to 18 mg/m2/day by bolus injection for three consecutive days. The dose limiting toxicity was leukopenia, and a maximally tolerated dose was 18 mg/m2/day (day 1-3). The recommended dose and schedule for a phase II study is determined to be 12 mg/m2/day for three consecutive days at 3-4 weeks intervals. Among non-hematologic toxicities, nausea and vomiting were severe, but stomatitis and alopecia were rarely observed. Clinical signs of cardiotoxicity were not seen.

Topics: Aged; Antibiotics, Antineoplastic; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Carubicin; Drug Evaluation; Female; Hodgkin Disease; Humans; Leukopenia; Lung Neoplasms; Male; Middle Aged; Thrombocytopenia

Cytotoxic activity of doxorubicin, daunomycin, carminomycin and ruboxyl against 50 human breast cancer heterotransplants in diffusion chambers was studied. The effect was estimated autoradiographically on the 6th or the 7th day of the cultivation after the drug administration in the maximum tolerance doses. The tumors were considered sensitive when the labeling index of their transplants after the treatment appeared to be reduced by 50 or less per cent against the control. The number of the tumors sensitive to all the drugs amounted to 72-80 per cent. 19 tumors were sensitive to 4 antibiotics. 14 and 8 tumors were sensitive to 3 and 2 antibiotics, respectively, and only 1 tumor was sensitive to 1 drug. The sensitivity significantly correlated with the initial labeling index of the primary tumors and their heterotransplants. The results suggested that daunomycin and ruboxyl possessed a high cytotoxic activity close to that of doxorubicin and carminomycin and might be recommended for clinical trials in the treatment of patients with breast cancer.

Topics: Animals; Breast Neoplasms; Carubicin; Cell Division; Daunorubicin; Diffusion Chambers, Culture; Doxorubicin; Female; Humans; In Vitro Techniques; Mice; Peritoneal Cavity; Transplantation, Heterologous

The anticancer activity of carminomycin was investigated in a human tumor cloning assay. No efficacy could be identified in the WiDr and the MCF7 cell lines which were highly responsive to doxorubicin. In addition, drug testing experiments were carried out in samples of various malignancies freshly obtained from 86 patients of whom 54 had not received prior anthracyclines. A reduction in the number of tumor colony forming units by 50% or more was seen in 1/26 breast cancers, 1/22 ovarian cancers and 1/7 melanomas. Cross-resistance studies indicated that eight tumors were responsive to doxorubicin only and one to carminomycin only whereas two were sensitive to both and 73 were resistant to both. This in vitro Phase II study corroborates the disappointing clinical results achieved with carminomycin.

Topics: Breast Neoplasms; Carubicin; Colony-Forming Units Assay; Daunorubicin; Doxorubicin; Drug Evaluation; Female; Humans; Melanoma; Ovarian Neoplasms; Tumor Stem Cell Assay

Carminomycin was administered to five patients at a dose of 7.5 mg/m2 twice weekly. Plasma and urine samples were obtained during two subsequent 72-hr periods following drug administration, and assayed for carminomycin (C) and carminomycinol (Col) by HPLC with fluorescence detection. Distribution of carminomycin was rapid and drug levels decreased below the detection limit (5 X 10(-9)M) within 24 hr. Carminomycinol appeared very quickly and surpassed carminomycin levels in 10 min-4 hr, disappearing very slowly, with a half-life of 40-98 hr. No major differences in pharmacokinetic behavior were found when comparing the five patients in this study with patients who received 18 mg/m2, as described in a previous report. After the second dose of carminomycin in the 7.5 mg/m2 twice weekly schedule, however, carminomycin pharmacokinetics were found to be altered in comparison with the first dose, the most pronounced difference being an increase in the t1/2 for Col from 65 +/- 28 to 173 +/- 81 hr.

Topics: Adult; Aged; Breast Neoplasms; Carubicin; Daunorubicin; Drug Administration Schedule; Female; Humans; Kinetics; Middle Aged

Twenty-two patients who had metastatic breast cancer previously treated with combination chemotherapy, cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) or CMF with vincristine and prednisone, were treated with Carminomycin (carubicin) 20 mg/m2 body surface area by intravenous bolus injection once every 3 weeks. Of 21 evaluable patients, 1 patient achieved complete remission, 5 patients achieved partial responses, and 11 remained stable. Cases of acute drug toxicity included myelosuppression, phlebitis, and gastrointestinal symptoms; there were four cases of mild alopecia, which consisted of thinning of the scalp hair. There were three cases of biopsy-proven cardiomyopathy, contrary to previous reports from the United Soviet Socialist Republic, which indicated that this drug was relatively free of cardiotoxicity. The median duration of remission for responders was 23 weeks. It is believed that Carminomycin has significant activity against metastatic breast cancer and, because its side effects, especially nausea, vomiting, and alopecia, were considerably milder than those experienced with Adriamycin, further investigation of this drug is warranted.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carubicin; Cyclophosphamide; Daunorubicin; Drug Evaluation; Female; Fluorouracil; Humans; Methotrexate; Middle Aged; Myeloproliferative Disorders; Prednisone; Time Factors; Vincristine

A total of 203 out patients with disseminated cancer of the mammary glands subjected to chemotherapy were followed up. Of these, 44 patients were treated according to the CMFVP program, 66 were subjected to monochemotherapy with carminomycin, 42 were treated with combinations of carminomycin and dibromdulcytol, 14 patients received monochemotherapy with adriamycin and 37 polychemotherapy according to the scheme of fluorouracil + adriamycin + cyclophosphamide. In addition to the early-demonstrated efficacy of adriamycin and the Cooper scheme, the comparative estimation of the treatment programs showed that carminomycin, a new antitumor antibiotic made in the USSR, had an obvious activity when used alone or in combination with dibromdulcytol, an alkylating agent, in the treatment of primary extended forms, relapses and metastases of mammary tumors. The data indicate that wide use of carminomycin which is comparatively low toxic is advisable in the treatment of disseminated cancer of the mammary gland.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carubicin; Cyclophosphamide; Daunorubicin; Doxorubicin; Fluorouracil; Humans; Methotrexate; Neoplasm Metastasis; Prednisone; Vincristine

In 9 patients with advanced malignant disease who received carminomycin (CMM) in an i.v. bolus injection (dose 18 mg/m2), curves of plasma concentrations of CMM and carminomycinol (CMMOH), a metabolite, versus time were constructed. For determination of plasma concentrations, high pressure liquid chromatography was used. For CMM and CMMOH the median areas under the curves (AUC's) were 31 (range 4-57) X 10(-8) mol/Ql/hr (measured over 24 hr) and 100 (range 309-158) X 10(-8) mol/l/hr (measured over 48 hr) respectively. From the data an accumulation of CMMOH in patients receiving treatments separated by brief intervals ban be predicted (half-life time of plasma disappearance for CMMOH was 2 days). Clinical toxicity was lowest in those 3 patients showing the lowest AUC for both CMM and CMMOH.

Topics: Breast Neoplasms; Carubicin; Chromatography, High Pressure Liquid; Daunorubicin; Humans; Sarcoma; Soft Tissue Neoplasms; Time Factors

Determination of polyamines (putrescine, spermidine) can be useful for evaluation of treatment efficacy. The amount of putrescine and spermidine were estimated for 10 patients (breast carcinoma; stage IV; T0--4 N0--3 M1) prior to, during and after different combination chemotherapy (carminomycin-dibromodulcitol; cyclophosphamide-methotrexate-5-fluorouracil). Hydrolysis with hydrochloric acid showed best results. Automated ion exchange chromatography is a sensitive and reproducible method. 6 out of 10 patients did not show both clinical changes and changes in polyamine content comparable to values prior to combination chemotherapy. One example demonstrated both clinical progression and an increase of polyamine content. A correlation between decrease of putrescine and spermidine level and clinical remission were found in 3 out of 10 patients. These results support the usefulness of polyamine determinations to evaluate cancer chemotherapy.

Topics: Breast Neoplasms; Carubicin; Cyclophosphamide; Fluorouracil; Humans; Methotrexate; Mitolactol; Polyamines; Putrescine; Spermidine

Thirteen patients with neglected mammary cancer were treated with karminomycin in combination with hexamethylmelamine. Twelve out of the 13 patients were previously subjected many times to cytostatic and hormonal therapy. A significant therapeutic effect was registered in 5 out the 13 patients (38 per cent), the total rate of the objective effect being 54 per cent. The remission period with a significant effect was 6 to 9 months. Fifteen patients with sarcoma metastases in the soft tissue were treated with karminomycin in combnation with methotrexate and cyclophosphane. A significant therapeutic effect was observed in 45 per cent of the cases with synovial sarcoma, hemangyopericitoma and leuomyosarcoma, the remission period being 4 to 12 months. The side effects of the above combinations were determined.

Topics: Aged; Altretamine; Antibiotics, Antineoplastic; Breast Neoplasms; Carubicin; Cyclophosphamide; Drug Therapy, Combination; Female; Humans; Lymphatic Metastasis; Methotrexate; Middle Aged; Neoplasm Metastasis; Sarcoma; Soft Tissue Neoplasms