Effects of ghrelin administration during chemotherapy with advanced esophageal cancer patients

A prospective, randomized, placebo-controlled phase 2 study

Authors

  • Yuichiro Hiura MD,

    1. Division of Gastroenterological Surgery, Department of Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
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  • Shuji Takiguchi MD, PhD,

    Corresponding author
    1. Division of Gastroenterological Surgery, Department of Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
    • Division of Gastroenterological Surgery, Department of Surgery, Graduate School of Medicine, Osaka University, 2-2, E2, Yamadaoka, Suita, Osaka 565-0871, Japan
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    • Fax: (011) 81-6-6879-3259

  • Kazuyoshi Yamamoto MD, PhD,

    1. Division of Gastroenterological Surgery, Department of Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
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  • Tsuyoshi Takahashi MD, PhD,

    1. Division of Gastroenterological Surgery, Department of Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
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  • Yukinori Kurokawa MD, PhD,

    1. Division of Gastroenterological Surgery, Department of Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
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  • Makoto Yamasaki MD, PhD,

    1. Division of Gastroenterological Surgery, Department of Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
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  • Kiyokazu Nakajima MD, PhD,

    1. Division of Gastroenterological Surgery, Department of Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
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  • Hiroshi Miyata MD, PhD,

    1. Division of Gastroenterological Surgery, Department of Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
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  • Yoshiyuki Fujiwara MD, PhD,

    1. Division of Gastroenterological Surgery, Department of Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
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  • Masaki Mori MD, PhD,

    1. Division of Gastroenterological Surgery, Department of Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
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  • Kenji Kangawa MD, PhD,

    1. Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka, Japan
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  • Yuichiro Doki MD, PhD

    1. Division of Gastroenterological Surgery, Department of Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
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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. Cancer 2012. © 2012 American Cancer Society.

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