Mitomycin C combination therapy against murine tumor systems: Effectiveness with cyclophosphamide and methotrexate

Abstract

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.

A new zebrafish model for experimental leukemia therapy

“…[20][21][22][23][24] In particular, the typical feature of both ZL1 and P388 leukemic lines is fast and synchronous death of the inoculated animals with median survival 9-13 d, quick dissemination of tumor growth and development of ascites in the terminal stage of leukemia. Moreover, the effective therapeutic doses of CY in the murine model are 100-400 mg/kg vs. 200-400 mg/L in fish and for VCR-0.1-2.5 mg/kg in mice vs. 2.5-4 mg/L in fish.…”

The Position of Combination Chemotherapy with Mitomycin C and Methotrexate in the Treatment of Metastatic Breast Cancer - Especially Triple Negative Breast Cancer

“…The synergistic effect of MMC and MTX was demonstrated in murine tumor systems, in which a considerable increase in activity was observed [38]. Recently, several studies on drug delivery systems have focused on the combination of MMC and MTX [39,40].…”

Combination Chemotherapy of Mitomycin C and Methotrexate Was Effective on Metastatic Breast Cancer Resistant to Eribulin, Vinorelbine, and Bevacizumab after Anthracycline, Taxane, and Capecitabine

“…The efficacy of MMC/MTX would be attributed to no cross-resistance with previous treatment. In addition, a synergistic effect of MMC and MTX was reported [ 5 , 6 , 7 ].…”