Combination chemotherapy against B 16 melanoma: bleomycin/vinblastine, bleomycin/cis-diamminedichloroplatinum, 5-fluorouracil/BCNU and 5-fluorouracil/methyl-CCNU

Abstract

Four antitumor drug combinations which are currently in clinical use were evaluated experimentally using the murine B 16 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 B 16, 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.Cancer 42: 171 1 -1719, 1978.OUR COMBINATIONS CHOSEN FOR analysis F in this report are of particular interest since they are currently being used clinically in the treatment of human solid tumors. The rationale for the conduct of clinical trials with these combinations has been that the regression rates for these drugs alone have been substantial, while their side effects were of different types and occurred at different times. The expectation was that the combinations of agents might produce increased therapeutic benefits without compounding toxicity.One combination tested was bleomycin (NSC 125066) and vinblastine (NSC 49842). Bleomycin is active as a single agent against testicular cancers,21,22 and is a good candidate for combination chemotherapy due to its lack of myel~suppression

The effect of lithium chloride on tumour appearance and survival of melanoma-bearing mice

“…Vinblastine, by disrupting the mitotic spindle temporarily increases the population of cells in the mitotic phase. Therefore it has been speculated that a combination of these two agents may have a more potent cytotoxic effect than that observed when each agent is used alone (Mabel et al, 1978). The combined treatment with both cytotoxic drugs and lithium chloride in melanoma-bearing mice produced in our hands a significant delay in tumour appearance, a higher degree of tumour necrosis and a longer survival rate.…”

“…In our experimental model we used a combination of vinblastine and bleomycin. This mode of treatment was found to be superior to other combinations such as bleomycin/cis-platinum, 5 Fluorouracil/BCNU and 5 Fluorouracil/methyl CCNU in the treatment of B16 melanoma in mice (Mabel et al, 1978).…”

“…The experiments were carried out in C57 BL adults female syngeneic mice, kept 10 to a cage in the animal house of the "Life Sciences Faculty", at (Mabel et al, 1978;Stephens et al, 1978 tumour appearance was observed in Group 3, when compared to groups 1 and 2 (P<0.05), and group 4 differed significantly in this parameter from group 3 (P<0.05) and from groups 1 and 2 (P<0.01).…”

The effectiveness of cis-platinum, cyclophosphamide and melphalan in treating disseminated tumor cells in mice

“…However, the drug injected as a single treatment at 8 mg/kg or in fractionated schedule (total dose of 7"3 mg/kg) significantly inhibited growth of LLC in other studies (15,36]. Fractionated treatment with a total dose of 12 mg/kg of the drug increased the median life span of B16M-bearing mice [18] and was effective against LLC or B16M in other reports [34,36]. Fractionated treatment with a total dose of 12 mg/kg of the drug increased the median life span of B16M-bearing mice [18] and was effective against LLC or B16M in other reports [34,36].…”

Complete response of huge buccal malignant melanoma in an octogenarian patient to arterial chemotherapy

“…Admittedly, most indications for intra‐arterial chemotherapy were thought to be palliative . Fluorouracil and cisplatin, however, have been reported to be active against malignant melanoma . In this study, we present the case of an octogenarian with primary unresectable buccal melanoma who received intra‐arterial infusion chemotherapy.…”