Exogenous nutrient administration has been shown to significantly stimulate tumor growth in numerous animal models. The present study was performed to determine if substrate-induced alterations in tumor metabolism could be exploited to potentiate tumor response to cycle-specific chemotherapy. Following subcutaneous mammary tumor (AC-33) implantation, 55 female Lewis/Wistar rats were randomly assigned to one of three nutritional regimens for 48 hr: (1) protein-depleted chow (0.03% protein) ad lib per os, (2) standard rat chow (22.0% protein) ad lib per os, or (3) total parenteral nutrition (TPN; 18.6% dextrose/2.8% amino acids). One-half of the animals in each group received a single dose of methotrexate (5 mg/kg im) while the remaining animals received placebo (saline) injections. At sacrifice, methotrexate-treated animals receiving TPN demonstrated a significantly smaller tumor volume (0.47 ± 0.44 cm3) compared to animals given either protein depleted chow (1.30 ± 0.76 cm3) or standard rat chow (1.34 ± 0.83 cm3) (P < 0.01). In this animal model, adjuvant TPN was found to significantly potentiate tumor response to cycle-specific chemotherapy with no detectable exacerbation of host toxicity.
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