Fall in plasma ghrelin concentrations after cisplatin-based chemotherapy in esophageal cancer patients

Abstract

Chemotherapeutic agents, especially cisplatin, cause severe gastrointestinal disorders, including nausea, vomiting, and anorexia, which markedly impair quality of life and encourage discontinuation of chemotherapy. Since cisplatin was recently reported to decrease plasma ghrelin and food intake in rodents, we monitored the plasma ghrelin level and its association with nutritional status and adverse events during chemotherapy in patients with esophageal cancer. Twenty patients with advanced esophageal cancer who underwent cisplatin-based neoadjuvant chemotherapy were enrolled in a prospective observational study. Changes in gastrointestinal hormones including ghrelin were measured and correlated with feeding activity, including appetite and dietary intake, nutritional status including rapid turnover proteins, and adverse events from chemotherapy. Plasma total ghrelin significantly decreased at days 3 and 8 of chemotherapy but recovered at day 28 (baseline: 140 ± 54; day 3: 107 ± 46; day 8: 82 ± 32; day 28: 126 ± 43 fmol/ml; p = 0.023 for day 3 and p = 0.034 for day 8). No changes were noted in plasma leptin (baseline: 3.2 ± 1.8; day 8: 2.5 ± 1.5 ng/ml; p = 0.18). Among blood nutritional parameters, transferrin was the only parameter that decreased significantly and its decline, as well as loss of oral intake and appetite, correlated significantly with plasma ghrelin levels (p = 0.0013, p = 0.0063, and p = 0.013, respectively). Neutropenia and anorexia were more frequent in patients with low plasma ghrelin than in those with high plasma ghrelin (p = 0.015 and p = 0.011, respectively). Cisplatin-based chemotherapy significantly reduced plasma ghrelin and feeding activity. Ghrelin is a potentially useful novel therapy for minimizing the adverse effects of chemotherapy.