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Blood, Vol. 92 No. 7 (October 1), 1998:
pp. 2471-2476
From the Departments of Medicine and Pharmacology and the Vermont
Cancer Center, University of Vermont, Burlington, VT.
The effect of folate status on the efficacy and toxicity of
chemotherapy was investigated in weanling Fischer 344 rats maintained on diets of varying folate content or supplemented with daily injections of folic acid, 50 mg/kg, for 6 to 7 weeks. MADB106 rat
mammary tumor growth rate 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 survival were observed
for cyclophosphamide (P = .0084) and 5-FU (P = .025) related to dietary folate content. Thus, folate deficiency
impedes tumor growth rate, but supplementation does not accelerate it in folate replete animals. Correction of folate deficiency
approximately doubles the efficacy of cyclophosphamide in rats with
much less host toxicity. Folate repletion improves survival in
5-FU-treated animals. These studies indicate that nutritional folate
status has an important influence on the efficacy and toxicity of some commonly used cancer chemotherapeutic drugs.
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