Therapeutic consequences of antitumour drug interactions: methotrexate and 5-fluorouracil in the chemotherapy of C3H mice with transplanted mammary adenocarcinoma.

Methotrexate and 5-fluorouracil at fixed dosages of 1.5 mg/kg and 50 mg/kg, respectively, were employed in combination chemotherapy for transplanted mammary adenocarcinoma in C3H mice. Tumour regression analyses demonstrated the importance of drug sequence and scheduling. Significantly, a drug synergism and antagonism was exhibited under certain conditions. Results indicated a superior therapeutic efficacy when methotrexate was administered 6-12 h before 5-fluorouracil; the reverse proved antagonistic. However, at longer intervals a commutative additivity was apparent. Judicious scheduling of methotrexate and 5-fluorouracil would seem appropriate, as both drugs are widely employed in the current management of neoplasms, such as breast carcinoma.