NUTRITIONAL FOLATE STATUS INFLUENCES THE EFFICACY AND TOXICITY OF CHEMOTHERAPY IN RATS

The effect of folate status on the efficacy and toxicity of chemothera py was investigated in weanling Fischer 344 rats maintained on diets o f varying folate content or supplemented with daily injections of foli c acid, 50 mg/kg, for 6 to 7 weeks. MADB106 rat mammary tumor growth r ate was the same in folate replete and supplemented rats, but retarded in the low folate groups, The tumor growth inhibitions in low folate, replete and high folate rats treated with cyclophosphamide were: 53%, 98%, and 97% (P=.048); with 5-fluorouracil (5-FU): 46%, 49%, and 66%; and with doxorubicin: 25%, 55%, and 61%, Significant differences in s urvival were observed for cyclophosphamide (P =.0084) and 5-FU (P =.02 5) related to dietary folate content. Thus, folate deficiency impedes tumor growth rate, but supplementation does not accelerate it in folat e replete animals. Correction of folate deficiency approximately doubl es the efficacy of cyclophosphamide in rats with much less host toxici ty, Folate repletion improves survival in 5-FU-treated animals. These studies indicate that nutritional folate status has an important influ ence on the efficacy and toxicity of some commonly used cancer chemoth erapeutic drugs. (C) 1998 by The American Society of Hematology.