食道がん化学療法中のグレリン投与

食道がん化学療法中のグレリン投与の効果をみたPhase2のランダム化比較試験を紹介します。

Hiura Y, Takiguchi S, Yamamoto K, Takahashi T, Kurokawa Y, Yamasaki M, Nakajima K, Miyata H, Fujiwara Y, Mori M, Kangawa K, Doki Y. 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.

リサーチクエスチョンは以下の通りです。

P：食道がんでシスプラチンの化学療法を行っている患者に
I：合成ヒトグレリン(3μg/kg)を1日2回1週間、静脈投与すると
C：プラセボと比較して
O：経口摂取エネルギー量が増加する
D：ランダム化比較試験

結果ですが、グレリン投与群で経口摂取エネルギー量は有意に増加しました(18.2kcal/kg/day vs 12.7kcal/kg/day）。食欲のVASスコアもグレリン投与群で有意に高かったです。化学療法中の副作用、QOL低下、吐気・嘔吐、全般的健康状態悪化は、グレリン投与群のほうが少なかったです。

グレリン投与を中止したのは21人中、大量発汗を認めた患者1人のみです。以上より、食道がんでシスプラチンの化学療法を行っている患者への短期のグレリン投与は、経口摂取エネルギー量を増加させ副作用を少なくするという結論です。

1週間のみの使用ですので、体組成の変化や筋力の変化は評価していません。経口摂取エネルギー量の増加は意味がありますが、静脈栄養とリハを適切に併用で体重変化に差は出ないかもしれません。サルコペニアや悪液質の改善に化学療法中（～後）のグレリンが有効か知りたいですね。

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.