Effects of ghrelin administration during chemotherapy with advanced esophageal cancer patients: a prospective, randomized, placebo-controlled phase 2 study

Cancer. 2012 Oct 1;118(19):4785-94. doi: 10.1002/cncr.27430. Epub 2012 Jan 26.

Abstract

Background: Cisplatin reduces plasma ghrelin levels through the 5-hydroxytryptamine (5-HT) receptor. This may cause cisplatin-induced gastrointestinal disorders and hinders the continuation of chemotherapy. The authors of this report conducted a prospective, randomized phase 2 trial to evaluate the effects of exogenous ghrelin during cisplatin-based chemotherapy.

Methods: Forty-two patients with esophageal cancer who were receiving cisplatin-based neoadjuvant chemotherapy were assigned to either a ghrelin group (n = 21) or a placebo group (n = 21). They received either intravenous infusions of synthetic human ghrelin (3 μg/kg) or saline twice daily for 1 week with cisplatin administration. The primary endpoint was changes in oral calorie intake, and the secondary endpoints were chemotherapy-related adverse events; appetite visual analog scale (VAS) scores; changes in gastrointestinal hormones and nutritional status, including rapid turnover proteins, and quality of life (QoL) estimated with the European Organization for Research and Treatment of Cancer QoL core questionnaire (QLQ-C30).

Results: Two patients were excluded from the final analysis: One patient suspended ghrelin administration because of excessive diaphoresis, and another patient in the placebo group failed to monitor the self-questionnaire. Food intake and appetite VAS scores were significantly higher in the ghrelin group than in the placebo group (18.2 ± 5.2 kcal/kg/day vs 12.7 ± 3.4 kcal/kg/day [P = .001] and 6.2 ± 0.9 vs 4.1 ± 0.9 [P < .0001], respectively). Patients in the ghrelin group had fewer adverse events during chemotherapy related to anorexia and nausea than patients in the control group. Significant deterioration was noted after chemotherapy in the placebo group in QoL scores, appetite, nausea and vomiting, and global health status.

Conclusions: Short-term administration of exogenous ghrelin at the start of cisplatin-based chemotherapy stimulated food intake and minimized adverse events.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Appetite / drug effects*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / physiopathology
  • Cisplatin / adverse effects
  • Energy Intake / drug effects*
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / pathology
  • Esophageal Neoplasms / physiopathology
  • Female
  • Ghrelin / administration & dosage
  • Ghrelin / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Nausea / chemically induced
  • Nausea / prevention & control
  • Neoadjuvant Therapy / methods
  • Neoplasm Staging
  • Patient Selection
  • Prospective Studies
  • Quality of Life*
  • Surveys and Questionnaires
  • Treatment Outcome
  • Vomiting / chemically induced
  • Vomiting / prevention & control

Substances

  • Ghrelin
  • Cisplatin