Although protein-energy malnutrition is common in the cancer patient, the efficacy of aggressive nutritional therapy is unclear. This study evaluates the effects of protein deficiency on tumor growth, response, and chemotherapy complications in primary and metastatic rat hepatoma. Seventy-two ACI rats (200-250 g) with implanted Morris hepatoma were divided into four groups (N = 18 for each group): 1, regular diet; 2, regular diet plus cyclophosphamide (CPM) (100 mg/kg/ip); 3, protein-free diet; and 4, protein-free diet + CPM. Forty additional rats in similar groups (5-8, ten in each group) underwent intravenous injection of 6 × 103 tumor cells to produce pulmonary metastases. Animals were assessed for survival, tumor size, serum albumin, number of pulmonary metastases, and hemorrhagic cystitis at 2 weeks. Survival was 50% in groups 4 and 8, and 100% in the others. Serum albumin was significantly lower in rats on protein free diets (2.59 ± 0.37 vs 3.35 ± 0.40 g%, P < 0.01). Tumor volume was significantly reduced by CPM (26.0 ± 4.2 cm3 vs 1.2 ± 0.4 cm3, P < 0.01). Protein-free diets resulted in lower total body weight, and reduced tumor volume without, but not with CPM (14 ± 1.6 cm3P < 0.05, 1.1 ± 0.3 cm3, P < 0.05 vs above controls). CPM reduced the number of pulmonary metastases in regular diet groups (307.2 ± 108.3 vs 36 ± 11, P < 0.01), while protein free diets did not significantly affect metastases, without or with CPM (251.7 ± 71.4 and 22.3 ± 12.4, P > 0.05 vs controls). Hemorrhagic cystitis was much more common in protein free groups compared to rats on regular diets (55 vs 11%, P < 0.01). These data indicate that protein deficiency did not affect response to chemotherapy in a primary or metastatic rat hepatoma model. However, protein deficiency results in a significantly increased rate of mortality, weight loss, and hemorrhagic cystitis which may lead to delay or cessation of cancer therapy.
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