Altered Metabolism and Mortality in Patients With Colon Cancer Receiving Chemotherapy

[American Journal of the Medical Sciences 310:48-55, 1995]

JOHN A. TAYEK, MD, FACP, FACN, LYNDA SUTTER, BS, SAVITA MANGLIK, MBBS, LINDA B. LILLINGTON, RN, PHD, MARY GROSVENOR, RD, MS, ROWAN T. CHLEBOWSKI, MD, PHD

ABSTRACT: To identify the metabolic effects of 5-fluorouracil and hydrazine sulfate therapy, 22 patients with colon cancer were admitted prospectively to a Clinical Research Center for serial measurement of counter-regulatory hormones, fasting hepatic glucose production (HGP), intravenous glucose tolerance test, plasma leucine appearance (LA) and leucine oxidation. Combined therapy was associated with a significant reduction in fasting glucose level (98±2 mg/dL to 94±2, P < 0.025) without a significant fall in fasting HGP (2.09±0.11 mg/kg/min versus 2.03±0.13; P >0.05). The decreased fasting glucose value was associated with a mild but not statistically improved glucose disposal rate in response to the intravenous glucose tolerance test (1.34±0.07 %/min vs 1.47±0.11, P = 0.15). Plasma leucine appearance was significantly reduced after 2 months of therapy (63.3±3.0mmol/kg/hr vs 57.1±3.9mmol/kg/hr; P < 0.025), but leucine oxidation (11.5±1.1 mmol/kg/hr vs 11.2±1.1 mmol/kg/hr) was not altered. Despite the fact that plasma triiodothyronine concentrations significantly increase with therapy, it was not associated with plasma LA. Half of the patients with cancer died 14±4 months after the study, and the other half were alive 58±2 months later. Survival time can be estimated with 59% accuracy using plasma LA, HGP, carcino-embryonic antigen, and insulin concentration. Multiple regression analysis identified that plasma LA was related directly to length of survival time, and baseline HGP, carcino-embryonic antigen, and insulin concentration were related inversely to length of survival. Unlike an elevated HGP seen in cancer cachexia, based on the association of a higher plasma LA and longer survival rate, an elevation in plasma LA and longer survival rate, an elevation in plasma LA may not be an unfavorable response to cancer. Further research is required to validate the predictability of baseline metabolic markers with survival rate in the cancer population. KEY INDEXING TERMS: Cancer cachexia; Hepatic glucose production; Plasma leucine appearance; Leucine oxidation; Hydrazine sulfate; Growth hormone; IGF-1; Cortisol; Glucagon; Colorectal carcinoma; Survival; Urine urea; Triiodothyronine. [Am J Med Sci 1995; 310(2):48-55.]

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