The in vivo response of a C3H mammary carcinoma to treatment with misonidazole, cyclophosphamide and radiation.

The potential chemosensitizing effect of the nitroaromatic radiosensitizer misonidazole (MISO) on the alkylating agent cyclophosphamide (CTX), and the interactions of these agents with radiation, have been investigated in a C3H mammary carcinoma in CDF1 mice. MISO at 1,000 mg/kg caused a small increase in tumour growth time (TGT; time to reach 3 times treatment volume) from 3.6 days to 4.5 days. CTX (100 mg/kg) increased the TGT to 15.7 days. The combined treatment of MISO and CTX given with intervals of either 15 min or 4 h increased the TGT to 23.3 and 23.8 days respectively. The radiation enhancement ratio (ER) was found to be 2.13 and 1.10 for MISO administered before or after x-rays respectively. The corresponding ERs for CTX were 1.16 and 1.22. The two drugs given in combination resulted in significant radiation ERs of 2.68 (both drugs given within 30 min before x-rays), 3.00 (MISO 30 min before and CTX 3 1/2 h after x-rays) and 1.40 (both drugs given after x-rays). In contrast to what has previously been reported, and in contrast to the tumour regrowth delay data, the results of the tumour control experiments were found to reflect no more than an additive action of the two drugs when used together with radiation in vivo.