Chemotherapy in combination with pelvic irradiation: a time-dependence study in mice

The importance of timing of drug administration in combination with pelvic irradiation on animal lethality was investigated in male CBA mice. The chemotherapeutic agents cyclophosphamide, cytosine arabinoside, 5-fluorouracil, methotrexate, cis-dichlorodiammine platinum (II), adriamycin, CCNU, VP-16 and bleomycin were administered at various times up to 2 weeks before and 2 weeks after pelvic irradiation (4 weeks before and after in the case of cyclophosphamide) of unanaesthetised mice and the LD50/30 days and dose enhancement factors determined. The results indicate a potentiation of radiation-induced damage when drugs are given near to the time of irradiation, particularly at about 3 days post-irradiation.