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.
D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D008727:Methotrexate / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D013997:Time Factors
D005472:Fluorouracil; D008727:Methotrexate