METABOLIC RESPONSE TO CHEMOTHERAPY IN COLON CANCER-PATIENTS

The goal of this investigation was to identify the metabolic abnormalities in a group of colon cancer patients before and during 5-fluorouracil chemotherapy. Twenty-two colon cancer patients were prospectively enrolled into a Clinical Research Center for measurement of counter regulatory hormones, fasting hepatic glucose production (HGP), intravenous glucose tolerance test, plasma leucine appearance (LA), and leucine oxidation (LO). Both the cancer group and the normal volunteers were matched for nutrition status (109 +/- 5% of ideal body weight vs 104 +/- 4%, mean +/- SEM, respectively) and history of weight loss (6.3 +/- 2.6 kg us 4.4 +/- 4.8). Plasma growth hormone was significantly elevated in the colon cancer patients (3.22 +/- 0.62 ng/mL vs 0.73 +/- 0.18, p < .05) despite the fact that insulin-like growth factor-1 levels were not different. Plasma glucose, insulin, cortisol, glucagon, epinephrine, and norepinephrine levels were not significantly different than those of the normal volunteers. Fasting HGP rates were slightly but not significantly elevated in the group of colon cancer patients compared with the normal volunteers (2.09 +/- 0.11 mg/kg per minute vs 1.79 +/- 0.10, p = .10). Plasma LA was not significantly elevated in the colon cancer group (63.3 +/- 3.0 mumol/kg per hour vs 57.7 +/- 4.2; p = .25). Five days of continuous 5-fluorouracil chemotherapy was associated with a significant elevation in both the fasting glucose level (97 +/- 3 mg/dL vs 106 +/- 5, p < .05), and HGP (2.09 +/- 0.11 mg/kg per minute us 2.27 +/- 0.10; p < .05). The increased fasting glucose value was associated with an increase in the insulin response to the intravenous glucose tolerance test. LA was not affected by the chemotherapy infusion (63.3 +/- 3.0 mumol/kg per hour vs 58.4 +/- 3.0). In contrast, LO was significantly increased (11.5 +/- 1.1 mumol/kg per hour vs 13.0 +/- 1.0, p < .05) and leucine incorporation into protein was significantly decreased (51.2 +/- 2.7 mumol/kg per hour vs 45.4 +/- 2.7, p < .05) while the patients received chemotherapy. Evaluating all the the counter-regulatory hormone measurements demonstrated a significant correlation between the mean HGP and growth hormone levels (r = .446; p < .05). Twenty-four-hour growth hormone pulse frequency in a patient with diffuse carcinoma was 2.5 times the normal rate compared with a sex- and weight-matched normal volunteer. The HGP rate was increased from 1.7 mg/kg per minute to 2.12 mg/kg per minute in the cancer patient. Further work is in progress to identify the possible association between growth hormone physiology and the elevation in fastin HGP observed in cancer patients.