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

Mitomycin C (MMC) has been evaluated in combination with several antitumor agents. Full dose response curves were established for all drugs and drug combinations. Synergy was shown with MMC plus either cyclophosphamide (CYC) or methotrexate (MTX). In testing MMC and CYC against P388 leukemia, the combined treatment yielded a 75% rate of long‐term survivors at the optimal level, compared to no survivors at the optimal level of the best single agent, CYC, alone. There was no increased toxicity among the combination‐treated animals. Large increases in lifespan were obtained against L1210 and B16. Maximally tolerated doses of the single agents could be combined without increased toxicity. The combination of MMC and MTX was synergistic against ip L1210 and P388 leukemias. The responses of mice bearing L1210 to treatment on days 1, 5, and 9 respectively, were 42% ILS for 3.0 mg/kg MMC; 96% ILS for 15 mg/kg MTX; 172% ILS with four out of ten survivors for 3.0 mg/kg MMC plus 15 mg/kg MTX. MMC and adriamycin (ADR) were found to be synergistic against B16 melanoma at one schedule but not against another schedule, or against colon carcinoma 26. No improvements over optimal nontoxic single agent therapy were seen for chlorambucil, 5‐fluorouracil, dibromodulcitol, cis‐diaminedichloroplatinum or 4‐(9‐acridinylamino)methansulfon‐M‐anisidide. On the basis of these data, recommendations were made for clinical trials for MMC plus either CYC or MTX against lung, breast, and colon tumors.

No abstract

No abstract