Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four antitumor drug combinations which are currently in clinical use were evaluated experimentally using the murine B16 melanoma model. Bleomycin plus vinblastine produced an increase in life span over either of the two agents alone against both intraperitoneal and subcutaneous B16. This combination also resulted in a large number of long-term survivors. Bleomycin plus cis-platinum produced slight enhancement against subcutaneous B16, but showed no advantage against intraperitoneal B16. The combination of 5-fluorouracil plus methyl-CCNU significantly increased survival time against the intraperitoneal tumor, and produced long-term survivors as well. The combination of 5-fluorouracil plus BCNU was not more effective than BCNU or 5-fluorouracil alone. These data were compared with the degree of success reported from the clinics against a variety of solid human neoplasms.
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PMID:Combination chemotherapy against B16 melanoma: bleomycin/vinblastine, bleomycin/cis-diamminedichloroplatinum, 5-fluorouracil/BCNU and 5-fluorouracil/methyl-CCNU. 8 16

Nine established human melanoma tissue-cultured cell lines heterotransplanted in C57BL/6 "nude" mice were exposed to each of 4 chemotherapeutic agents of known clinical activity against human melanoma. Two of the therapeutic agents, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 5-(3,3-dimethyl-1-triazino) imidazole-4-carboxamide (DTIC), are known to be active against human melanoma; the other two, adriamycin and 5-azacytidine, are known to be inactive. Sterile saline served as a control agent. In 2 cell line heterotransplants, the control tumor spontaneously regressed. Of the 7 cell lines that remained for evaluation, 4 were sensitive to DTIC, 1 was sensitive to BCNU, and none was sensitive to adriamycin or 5-azacytidine. These data indicate that the nude mouse-human tumor model may be a predictive secondary screen for cancer chemotherapeutic agents.
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PMID:Evaluation of a "nude" mouse-human tumor panel as a predictive secondary screen for cancer chemotherapeutic agents. 9 97

The nitrosoureas (BCNU, CCNU, methyl CCNU) represent a new class of antineoplastic agents with a broad spectrum of antitumor activity. They are cell-cycle nonspecific cytotoxic agents. Postulated modes of action and pharmacology of these nitrosoureas are reviewed. Their therapeutic effectiveness as single agents and in combinations have been recognized in malignant lymphomas, multiple myeloma, melanoma, glioblastoma multiforme, gastric and colorectal carcionma, and small-cell carcinoma of the lung. The nitrosoureas are administered on an intermittent 6--8-week schedule because of delayed and frequently severe bone marrow toxicity which may be cumulative in nature.
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PMID:Nitrosoureas: a reappraisal of clinical trials. 39 66

Eighteen patients with refractory malignancies were treated with escalating doses of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and autologous bone marrow transplants (BMTX). Hematopoietic recovery was similar with doses of 300mg/m2qd X 3 and 500mg/m2qd X 3 providing suggestive evidence of a myeloprotective effect of the BMTX. Extramedullary toxicity was sporadic but occasionally severe; pulmonary fibrosis and severe cholestatic jaundice were seen in one case each. Antitumor responses were noted in patients with brain tumors, melanoma, hematological neoplasms and lung cancer.
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PMID:Intensive 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) autologous bone marrow transplantation therapy of refractory cancer: a preliminary report. 40 Jun 99

Thin slices of s.c. implanted B-16 melanomas as well as of human melanomas have been incubated for 5 h with (H3) Uridine and (H3) Thymidine in the presence of different chemotherapeutical agents, whose concentration was equivalent to the tenfold therapeutical daily dose in men. In this short term test model, the sensitivity of a melanoma to a chemotherapeutical agent is indicated by the inhibition of the nucleoside uptake by more than 50%. The in vitro sensitivity rates, each based on 10--30 melanomas, are compared to the in vivo sensitivity rates. Sensitivity is indicated by the increase of life span (greater than 25%) in the melanoma bearing mice respectively by the regression of human melanoma metastases (greater than 50%). -- The in vivo sensitivity of the B-16 melanomas, evaluated by the uridine and/or thymidine uptake, was in line with the in vivo sensitivity to all chemotherapeutical agents with the exeption of Adriamycine and DTIC. The in vitro sensitivity of human melanomas to Dactinomicine, Vincristine, BCNU and DTIC corresponds to the in vivo sensitivity whereas no in vitro/in vivo correspondence could be observed in testing Bleomycine, Procarbacine and 5-Fluorouracile. Comparing the sensitivity of B-16 and human melanomas, similarity was observed in vitro but not in vivo.
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PMID:[In vitro and in vivo sensitivity of animal and human melanomas to various chemotherapeutical agents]. 56 19

We describe in this paper cell survival studies, using in vitro clonogenic assays, performed on the B16 melanoma treated in situ with various cytotoxic agents. In addition we have determined the effects of these agents on the yield of cells obtained by trypsinization. In untreated tumours the mean cell yield was approximately 10(8)/g, which is 20--30% of the cells actually present in the tissue. The plating efficiency was approximately 40%. Most agents rapidly affected both cell yield and cell survival. For example, within 20--30 h, gamma-radiation and several alkylating agents reduced cell yield by about 40%. The cell yield change was associated with an increase in mean cell size. Cell yield was reduced even more (approximately 70%) by Vinca alkaloids. This large reduction was associated with extensive cell lysis, observed as an increase in the necrotic fraction of tumours from approximately 35% to approximately 70%. Adriamycin, bleomycin and Ara-C also produced a moderate reduction in cell yield (approximately 40%), but actinomycin D did not reduce cell yield and FU increased it by about 30%. Only gamma-radiation, cyclophosphamide, CCNU, BCNU and melphalan produced more than a 90% reduction in cell survival, although there was a small but measurable reduction with all other agents except vinblastine, HN2 and actinomycin D.
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PMID:Cell yield and cell survival following chemotherapy of the B16 melanoma. 72 48

The therapeutic usefulness of chlorpromazine (CPZ) and caffeine (CAF) in combination with selected nitrosoureas was investigated in mice bearing L1210 leukemia, Lewis lung carcinoma, and B16 melanoma. We found that using BCNU with either CAF or CPZ was therapeutically superior to using either agent alone to treat mice bearing L1210 leukemia. Administering all three drugs in combination did not improve upon the therapeutic responses obtained with the two-drug combinations. In mice implanted with Lewis lung carcinoma or B16 melanoma, responses to treatment with the triple combination of methyl-CCNU, CAF, and CPZ suggested, but did not clearly establish, superiority over each two-drug combination or methyl-CCNU alone.
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PMID:Therapeutic potentiation of nitrosoureas using chlorpromazine and caffeine in the treatment of murine tumors. 75 16

In a phase I study, the best antitumor/toxicity ratio for DTIC was reported to be at a dose of 250 mg/m2/day X 5 repeated at 28-day intervals. Nausea, vomiting, leukopenia, and thrombocytopenia were the major toxic effects noted. The best responses were seen in disseminated melanoma (19%), various sarcomas (22%), and Hodgkin's disease. A subsequent phase II study in refractory lymphomas showed a response rate in Hodgkin's disease of 56%. In disseminated melanomas, DTIC was then combined with vincristine and BCNU and demonstrated a response rate of 23% which did not improve with the addition of chlorpromazine (23%). A response rate of 31% was seen with the combination of DTIC, BCNU, and hydroxyurea which did not improve with the addition of vincristine (30%). Responders had a more significant survival rate as compared to nonresponders.
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PMID:DTIC (NSC-45388) studies in the southwest oncology group. 76 72

The results of three controlled studies with multiple-drug regimens which included DTIC are reported for advanced melanoma, soft tissue sarcomas, and Hodgkin's disease. In malignant melanoma, no statistical difference was observed between (a) DTIC, BCNU, and vincristine, and (b) DTIC, BCNU, and actinomycin D in terms of response rate, median duration of response, and survival. In sarcomas, the combination of adriamycin and DTIC produced a higher incidence of complete plus partial responders when compared to cyclophosphamide, vincristine, and methotrexate. However, no significant difference was seen in the median duration of response or survival. In Hodgkin's disease, a new four-drug combination including adriamycin, bleomycin, vinblastine, and DTIC (ABVD) produced an incidence of complete remissions and a median duration of response comparable to that achieved with mechlorethamine, vincristine (Oncovin), predinisone, and procarbazine (MOPP). Preliminary data indicate that ABVD is not cross resistant to MOPP. It is concluded that DTIC can be successfully and safely employed in combination with conventional agents in susceptible neoplastic diseases.
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PMID:Combination chemotherapy with DTIC (NSC-45388) in advanced malignant melanoma, soft tissue sarcomas, and Hodgkin's disease. 76 75

Three of the nitrosoureas, BCNU, CCNU, and methyl-CCNU, have displayed significant antitumor activity in patients with disseminated malignant melanoma with none clearly superior to the others, although direct comparison in clinical trials was not accomplished. Response rates to various combinations of these nitrosoureas seem a bit higher, but not dramatically so, when compared to the single-agent response rates, although again this cannot be stated with certainty since direct comparisons were not accomplished. There appears to be no therapeutic advantage to the utilization of any one of the nitrosoureas over the others, but oral administration, as is available for CCNU and methyl-CCNU, is a distinct advantage to the patient and to the clinician. The response rates are, for the most part, rather consistent for the various studies reported in this paper, and these response rates leave a great deal of room for improvement. Secondary therapy utilizing the nitrosoureas was singularly unsuccessful in most of the reported clinical trials. It is refreshing, however, to have agents which have shown activity, although modest, in this most refractory of neoplasms.
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PMID:Nitrosoureas in the management of disseminated malignant melanoma. 78 96


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