アナモレリンのがん悪液質治療効果

アナモレリン（経口投与可能なグレリン受容体作動薬）のがん悪液質患者に対する治療効果をみたパイロット研究を紹介します。

Garcia JM, Friend J, Allen S. Therapeutic potential of anamorelin, a novel, oral ghrelin mimetic, in patients with cancer-related cachexia: a multicenter, randomized, double-blind, crossover, pilot study. Support Care Cancer. 2012 Jun 16. [Epub ahead of print]

アナモレリンは以前、以下のブログで紹介しました。
anamorelinのグローバル第III相臨床プログラム開始
http://rehabnutrition.blogspot.jp/2011/09/anamoreliniii.html

今回はパイロット研究ですが、クロスオーバーのRCTです。アナモレリン1日50 mg3日間内服とプラセボを比較した結果、介入群で有意な体重増加が得られました (0.77 kg vs. -0.33 kg)。食事摂取量は増加しましたが、統計学的有意差を認めませんでした。

食欲は介入群で有意に改善しました。アナモレリンの副作用として、高血糖2人、吐気1人、めまい1人を認めましたが軽症でした。これよりアナモレリンは、がん悪液質患者に有効な可能性があり、さらなる研究が必要という結論です。

アナモレリンにはかなり期待していますが、3日間の使用でこれだけ差が出るものでしょうか。体重増加が筋肉量増加もしくは減少軽減で得られていればよいのですが、3日間で1kgの差では水分の影響も大きいのではという気がしてしまいます。身体組成と長期使用の効果も知りたいですね。

Abstract

PURPOSE:

Cachexia in cancer adversely affects patients' perception of symptoms, well-being, and response to therapy, and shortens survival. Anamorelin, an oral mimetic of ghrelin, has been shown to increase body weight and anabolic hormone levels in healthy volunteers and is being investigated to treat cancer cachexia.

METHODS:

This multicenter, double-blind, placebo-controlled, crossover study evaluated the effects of anamorelin in 16 patients with different cancers and cachexia. Patients were randomly assigned to anamorelin 50 mg/day or placebo for 3 days. A 3- to 7-day washout period followed and then treatments were switched. Assessments included body weight, appetite, food intake, growth hormone (GH) levels, patient-reported symptom assessments (e.g., the Anderson Symptom Assessment Scale [ASAS] and also an inclusion criterion), and safety.

RESULTS:

Anamorelin significantly increased body weight compared with placebo (0.77 kg vs. -0.33 kg). Food intake increased compared with placebo, but not significantly. GH significantly increased at all time points (0.5-4 h postdose). Insulin-like growth factor-1 (IGF-1) significantly increased by 54.09 ng/mL with anamorelin treatment compared with -3.56 ng/mL for placebo; significant changes in insulin-like growth factor-binding protein 3 (IGFBP-3) were 0.75 μg/mL vs. -0.19 μg/mL, respectively. Patient-reported symptoms, including appetite as measured by ASAS, significantly improved with anamorelin (8.1 vs. 1.0 for placebo). Adverse events (AEs) in four patients were possibly or probably related to anamorelin: hyperglycemia (two patients), nausea (one patient), and dizziness (one patient). Most AEs were mild; no patients withdrew due to AEs.

CONCLUSIONS:

Anamorelin showed significant metabolic, clinical, and patient-rated effects in cancer cachexia. Further studies are warranted.