Metabolism , and Physical Functioning Insulin Treatment in Cancer Cachexia : Effects on Survival , Updated

Purpose:The present studywas designed to evaluatewhether daily insulin treatment for weightlosing cancer patients attenuates the progression of cancer cachexia and improves metabolism and physical functioning in palliative care. Experimental Design:One hundred and thirty-eight unselected patients withmainly advanced gastrointestinalmalignancy were randomized to receive insulin (0.11F0.05 units/kg/d) plus best available palliative support [anti-inflammatory treatment (indomethacin), prevention of anemia (recombinant erythropoietin), and specialized nutritional care (oral supplements + home parenteral nutrition)] according to individual needs. Control patients received the best available palliative support according to the same principles. Health-related quality of life, food intake, resting energy expenditure, body composition, exercise capacity, metabolic efficiency during exercise, and spontaneous daily physical activity as well as blood tests were evaluated during follow-up (30-824 days) according to intention to treat. Results: Patient characteristics at randomizations were almost identical in study and control groups. Insulin treatment for 193F 139 days (meanF SD) significantly stimulated carbohydrate intake, decreased serum-free fatty acids, increased whole body fat, particularly in trunk and leg compartments, whereas fat-free lean tissue mass was unaffected. Insulin treatment improved metabolic efficiency during exercise, but did not increase maximum exercise capacity and spontaneous physical activity. Tumor markers in blood (CEA, CA-125, CA 19-9) did not indicate the stimulation of tumor growth by insulin; a conclusion also supported by improved survival of insulin-treated patients (P < 0.03). Conclusion: Insulin is a significant metabolic treatment in multimodal palliation of weight-losing cancer patients. Alterations in the classic hormone system are major effector mechanisms behind changes in whole body metabolism and nutritional state during tumor progression (1). Most hormones are involved, but insulin resistance appeared early as a presumable abnormality contributing to weight loss (2), although changes in the noradrenergic system (3), growth hormone/ insulin-like growth factor I (IGF-I) axis (4, 5), thyroid hormones, and glucocorticoids contribute, but additional hormones such as leptin, ghrelin, and other neuroendocrine factors are also important (6–9). Most hormonal changes are interrelated to other metabolic pathways as increased activities of eicosanoids, growth factors, and cytokines (10–12). Accordingly, our previous studies have confirmed clinical improvements by systemic anti-inflammatory treatment (13, 14), prevention of anemia (15), and nutritional support to patients with cancer (4). However, reevaluation of alterations in body composition in our cancer patients on multimodal treatment unexpectedly revealed that whole body fat, which predicts survival, was lost despite effective supportive care indicated by stable lean body mass during tumor treatment (8). Based on these and other observations, it seemed appropriate to consider antilipolytic treatment to attenuate cachexia progression. Consequently, a simple concept would be to treat weight-losing cancer patients with insulin as suggested half a century ago (16). Therefore, the present study was designed to evaluate whether daily treatment with long-acting insulin for weight-losing cancer patients would attenuate the progression of cancer cachexia and improve host metabolism without harmful side effects in unselected cancer patients. Materials andMethods