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Background. Cancer cachexia is associated with a decreased insulin:glucagon ratio. The authors hypothesized that the decrease in this anabolic hormone index is largely responsible for the progressive catabolism characteristic of cancer cachexia. Previous studies of insulin therapy alone in treating cancer cachexia have yielded limited success due to insulin-induced hypoglycemia and subsequent glucagon secretion. The current study was performed to determine the effect of combined hormone therapy (growth hormone, insulin, and somatostatin) on tumor growth, metastasis, and host metabolism. Methods. Twenty-four female Lewis/Wistar rats (175-200 g) were subcutaneously inoculated on the flank with the MAC-33 tumor, a spontaneously metastasizing mammary adenocarcinoma. Thirty days after tumor implantation, animals were randomized to receive combined hormone therapy or saline (control) injections. Hormone therapy consisted of recombinant growth hormone (1000 U/kg/day intraperitoneally [IP]), somatostatin analogue (SMS 201-995; 150 [mu]g/kg twice daily IP) and NPH humulin insulin (5 U/kg twice daily subcutaneously). Results. Triple hormone therapy with growth hormone, insulin, and somatostatin significantly increased host carcass weight (211 [+ or -] 4 g versus 179 [+ or -] 6 g; P < 0.01) and decreased tumor:carcass ratio (0.25 [+ or -] 0.03 versus 0.35 [+ or -] 0.05; P < 0.01). Hamstring muscle weight and protein content were significantly increased and tumor cellular protein content was decreased in animals receiving triple hormone therapy. A significant decrease in S-phase tumor cell cycle kinetics occurred in hormone-treated versus control animals. Conclusions. Thus, combined therapy of growth hormone, insulin, and somatostatin selectively supports host anabolism and inhibits tumor growth kinetics. Combined hormone therapy specifically improves skeletal muscle protein content and reduces tumor protein incorporation. This innovative metabolic therapy for cancer cachexia may be useful in the future to prevent the progressive catabolism present in the tumor-bearing host. Cancer 1994; 73:1499-504.