Effects of nutritional repletion on host and tumor response to chemotherapy

Host and tumor response to methotrexate (MTX) was studied in 122 tumor-bearing, malnourished rats during nutritional repletion. Sprague-Dawley rats with transplanted Walker-256 carcinosarcoma were fed a regular diet (RD) for five days followed by a protein-free diet (PFD) for ten days. On day 15, one group was orally repleted with a regular diet, while the other group continued on PFD. Methotrexate (20 mg/kg) therapy was begun in RD groups either on day 17 or day 21. Similarly, MTX (20 mg/kg) was begun in PFD groups either on day 17 or day 21. Untreated (no MTX) rats served as control animals and gained more body weight than MTX-treated rats. Tumor weight (TW) to carcass weight (CW) ratios were significantly less in both PFD and RD groups when MTX was given two days after dietary manipulation compared with results when MTX was given six days after dietary manipulation. Maximum tumor inhibition by MTX (least change in tumor diameter compared with control rats) was significantly greater when MTX was given to nutritionally repleted animals compared with results when MTX was given to animals continued on the protein-free diet. Dietary protein depletion inhibited tumor growth and tumor response to methotrexate. Nutritional repletion stimulated host and tumor growth. A short period of nutritional repletion (two days) prior to MTX chemotherapy resulted in improved host nutritional status and maximum tumor inhibition.