Interactions of radiation, cyclophosphamide and nimorazole in a C3H mammary carcinoma in vivo.
The combined effect of adjuvant Cyclophosphamide (CTX) and the hypoxic radiosensitizer, Nimorazole (NIM), on the radiation response was studied in a C3H mammary carcinoma in CDF1 mice. The effect of NIM and CTX alone or in combination without radiation was assessed by tumor growth delay measured by tumor growth time (TGT). Administration of CTX (100 mg/kg) increased the TGT from 5.2 days in untreated controls to 18.8 days. NIM (1000 mg/kg) had no effect on the TGT. The combined treatment with NIM given 4 hrs before CTX did not increase the TGT compared with CTX alone, which suggests that NIM does not potentiate CTX. The possible effect of an interaction between the therapeutic parameters was determined by administration of NIM, CTX, and radiation in different sequences to C3H mammary tumor bearing mice. The drugs were administered as single doses before or after graded single doses of irradiation. The end point was the radiation dose required to achieve local tumor control in 50% of the mice (TCD50). The enhancement ratio (ER)--defined as TCD50 for radiation alone relative to TCD50 for radiation combined with drug--was 1.2 for CTX given either 15 min before or 4 hrs after radiation. NIM given 30 min before radiation showed an ER of 1.6, but no enhancement was obtained when NIM was given after radiation. When NIM was given immediately after radiation, followed 4 hrs later by CTX, the ER was 1.2. However, applying NIM 30 min before radiation and CTX 3.5 hrs after radiation, the ER increased to 1.6. NIM given 30 min before, together with CTX given 15 min before radiation, showed an ER of 1.8. Our data suggest that: an improved tumor response may be expected when CTX is added to a radiation and hypoxic radiosensitizer treatment; this improvement is attributable to an additive effect based on the chemotherapy response alone rather than to chemopotentiation by the hypoxic radiosensitizer.
D000818:Animals; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000532:radiotherapy*; D051379:Mice; D009554:Nimorazole / Q000627:therapeutic use*; D009593:Nitroimidazoles / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*
D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D009554:Nimorazole; D003520:Cyclophosphamide