NEGATIVE IMPACT OF CANCER-CHEMOTHERAPY ON PROTEIN-METABOLISM IN HEALTHY AND TUMOR-BEARING RATS

Although chemotherapeutic agents are widely used in the treatment of c ancer, few experimental data are available on their effects on host N metabolism. We studied the effects of a single intraperitoneal (IP) in jection of cyclophosphamide ([CYP] 120 mg/kg), 5-fluorouracil ([5-FU], 50 mg/kg), cisplatinum ([CDDP], 5 mg/kg), or methotrexate ([MTX], 30 mg/kg). N balance was studied for 6 days following chemotherapy in hea lthy rats (0 = 40) and in rats bearing Morris Hepatoma 7777 ([MH7777] n = 40) in a situation comparable to that of human cancer (tumor burde n < 0.2% of body weight, moderate anorexia, and weight loss). In healt hy rats, all drugs induced transient body weight loss, anorexia, and p oor N balance. At day 6 posttreatment, all animals had resumed normal feed intake and positive N balance except CDDP-treated rats, which sho wed continued weight loss and poor N balance. CDDP and MTX exhibited a ntitumor activity; however, CDDP induced diarrhea in six of eight tumo r-bearing rats. Drug-induced anorexia was more severe in tumor-bearing than in healthy treated rats. N balance was more severely decreased i n MH7777-bearing rats than in healthy treated animals in response to 5 -FU (159 +/- 36 v 273 +/- 27 mg N/2 d) and MTX (-66 +/- 36 v 153 +/- 3 7 mg N/2d) at days 3 to 4 postinjection. These results establish the p resence of drug-specific effects on host N balance and the existence o f a drug-tumor interaction for N metabolism in the tumor-bearing host. Copyright (C) 1995 by W.B. Saunders Company