Effect of cytotoxic agents on protein kinetics in patients with metastatic cancer

Because marked body wasting frequently occurs in hospitalized cancer patients, we have assessed protein kinetics in patients with metastatic cancer undergoing chemotherapy. Seven male patients with histologically confirmed stage III testicular carcinoma were studied before and after administration of triple-drug chemotherapy (Vinblastine, Cis-platinum, and Bleomycin). All patients received continuous intravenous feedings to provide exactly 30 kcal/kg/day and 1 gm of protein/kg/day, and all excreta were collected to determine nitrogen balance before and after therapy. In five individuals the stable nonradioactive isotope, (15)N-labeled glycine, was added to the infusate. After adequate equilibration, urinary urea enrichment with (15)N was determined, and protein flux (Q), synthesis (S), and catabolism (C) were calculated by means of the model described by Picou and Taylor-Roberts. Nine studies in four age-matched normal individuals receiving similar nutritional support served as controls. This group of cancer patients maintained nitrogen balance when receiving adequate nutritional support prior to chemotherapy, as did the normal control subjects. However, following administration of chemotherapy, patients showed worsening of nitrogen balance in spite of maintenance of nutritional intake. Q, S, and C in the cancer patients with advanced testicular carcinoma prior to Course I of chemotherapy did not differ significantly from those values in the normal control subjects. The mean Q value in the cancer patient with disseminated disease was 38.8 ± 3.3 gm N/day and in the control group Q = 39.5 ± 2.5 gm N/day. The mean value for C and S in the cancer patient groups did not differ significantly from those values in the control subjects and reflected the overall nitrogen equilibrium of these patients. However, all three parameters, Q, S, and C, differed significantly from the prechemotherapy values. Following chemotherapy, the mean Q decreased 23%, the mean S value decreased 34%, and the mean C value decreased 30%. Throughout the entire study, nutritional intake was maintained. These studies emphasize the impact of cytotoxic therapy on disruption of lean body mass, supporting the concept that vigorous nutritional support is essential during aggressive cancer therapy.