Critical evaluation of the role of nutritional support with chemotherapy

Abstract

Although weight loss has an adverse impact on cancer patient survival, the ability of caloric provision via total parenteral nutrition (TPN) to favorably influence outcome in chemotherapy‐treated populations is not established. In randomized trials, no significant improvement in either response or survival was associated with TPN addition to chemotherapeutic treatment of adult patients with lymphoma, sarcoma, colon cancer, adenocarcinoma and small cell carcinoma of the lung, or testicular carcinoma. In two instances, TPN addition was associated with decreased survival, again raising the concern that caloric support in the absence of effective antitumor therapy might stimulate cancer growth. In any event, the hypothesis that nutritional repletion of a malnourished cancer patient receiving chemotherapy will improve clinical outcome remains to be critically tested, as studies demonstrating sequential improvement in lean body mass have not been reported. Most recently, consideration of potential mechanisms underlying the development of cancer cachexia has led to new strategies for nutritional intervention. For example, hypogonadism or low testosterone levels have been described in male patient populations with advanced cancer and correlated with weight loss and adverse outcome, leading to trial of replacement therapy with nandrolone decanoate. Similarly, the frequent identification of abnormal glucose metabolism in the patients with cancer cachexia has stimulated clinical trials with agents such as hydrazine sulfate and insulin designed to reverse the metabolic abnormality. Whether such efforts designed to alter metabolic abnormalities associated with cancer cachexia will improve clinical outcome will be determined in ongoing clinical trials.

Carnitine palmitoyltransferase II activity is decreased in liver mitochondria of cachectic rats bearing the Walker 256 carcinosarcoma: Effect of indomethacin treatment

“…Nutritional support alone failed to prevent weight losses (6) in patients and tumourbearing animals. Severe metabolic imbalance accompanies the cachectic condition, in a manner similar to that seen in sepsis and trauma (3).…”

“…BIOCHEMISTRYand MOLECULAR BIOLOGY INTERNATIONAL the fat mass, intestinal malabsorption, anorexia, and negative calorie and nitrogen balances (2,4,5). Nutritional support alone failed to prevent weight losses (6) in patients and tumourbearing animals. Severe metabolic imbalance accompanies the cachectic condition, in a manner similar to that seen in sepsis and trauma (3).…”

Suramin interferes with interleukin-6 receptor binding in vitro and inhibits colon-26-mediated experimental cancer cachexia in vivo.

“…Up to 50% of all patients have lost weight by the time of diagnosis, and nearly all patients who die from cancer exhibit wasting (6). Recent attempts to compensate, through total parenteral nutrition, for the negative caloric balance in patients failed to alter wasting (7). The mitigation of wasting by pharmacological intervention, therefore, is important not only because anticachexia therapy could improve the survival and quality oflife of the patient, but also because it could give way to a more effective anticancer therapy.…”

Cancer cachexia

“…It has been suggested (Studley, 1936) that 30% loss of body weight is invariably fatal, so attempts have been made to counter the weight loss in cancer patients by administering total parenteral nutrition (TPN). However, clinical studies giving extra calories via TPN have failed to alter the weight loss, and in at least two of the randomised TPN trials, a decreased survival was seen in the TPN treatment arm (Chlebowski, 1985). Since weight loss is one of the most common adverse systemic effects of malignancy occurring early in the course of the disease (De Wys, 1985), an understanding of the mechanism of cachexia could obviously benefit a large number of patients.…”