GROWTH-HORMONE, INSULIN, AND SOMATOSTATIN THERAPY OF CANCER CACHEXIA

Background. Cancer cachexia is associated with a decreased insulin:glu cagon ratio. The authors hypothesized that the decrease in this anabol ic hormone index is largely responsible for the progressive catabolism characteristic of cancer cachexia. Previous studies of insulin therap y alone in treating cancer cachexia have yielded limited success due t o insulin-induced hypoglycemia and subsequent glucagon secretion. The current study was performed to determine the effect of combined hormon e therapy (growth hormone, insulin, and somatostatin) on tumor growth, metastasis, and host metabolism. Methods. Twenty-four female Lewis/Wi star rats (175-200 g) were subcutaneously inoculated on the flank with the MAC-33 tumor, a spontaneously metastasizing mammary adenocarcinom a. Thirty days after tumor implantation, animals were randomized to re ceive combined hormone therapy or saline (control) injections. Hormone therapy consisted of recombinant growth hormone (1000 U/kg/day intrap eritoneally [IP]), somatostatin analogue (SMS 201-995; 150 mu g/kg twi ce daily IP) and NPH humulin insulin (5 U/kg twice daily subcutaneousl y). Results. Triple hormone therapy with growth hormone, insulin, and somatostatin significantly increased host carcass weight (211 +/- 4 g versus 179 +/- 6 g; P < 0.01) and decreased tumor:carcass ratio (0.25 +/- 0.03 versus 0.35 +/- 0.05; P < 0.01). Hamstring muscle weight and protein content were significantly increased and tumor cellular protei n 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 t herapy of growth hormone, insulin, and somatostatin selectively suppor ts host anabolism and inhibits tumor growth kinetics. Combined hormone therapy specifically improves skeletal muscle protein content and red uces tumor protein incorporation. This innovative metabolic therapy fo r cancer cachexia may be useful in the future to prevent the progressi ve catabolism present in the tumor-bearing host.