がん悪液質とカルニチン・セレコキシブ

がん悪液質に対するカルニチン＋セレコキシブ±酢酸メゲステロールの効果を見た非劣性RCT論文を紹介します。

Madeddu C, Dessì M, Panzone F, Serpe R, Antoni G, Cau MC, Montaldo L, Mela Q, Mura M, Astara G, Tanca FM, Macciò A, Mantovani G. Randomized phase III clinical trial of a combined treatment with carnitine + celecoxib ± megestrol acetate for patients with cancer-related anorexia/cachexia syndrome. Clin Nutr. 2011 Oct 31. [Epub ahead of print] doi:10.1016/j.clnu.2011.10.005

セレコキシブは、コキシブ系非ステロイド性抗炎症薬（COX-2選択的阻害）です。NSAIDですので抗炎症作用はもちろんありますが、抗異化作用があることも最近、報告されています。以下の文献が参考になります。

Lai V, George J, Richey L, Kim HJ, Cannon T, Shores C, et al. Results of a pilot study of the effects of celecoxib on cancer cachexia in patients with cancer of the head, neck, and gastrointestinal tract. Head Neck 2008;30:67e74.
Cerchietti LC, Navigante AH, Peluffo GD, Diament MJ, Stillitani I, Klein SA, et al. Effects of celecoxib, medroxyprogesterone, and dietary intervention on systemic syndromes in patients with advanced lung adenocarcinoma: a pilot study. J Pain Symptom Manage 2004;27:85e95.
Mantovani G, Maccio A, Madeddu C, Serpe R, Antoni G, Massa E, et al. Phase II nonrandomized study of the efficacy and safety of COX-2 inhibitor celecoxib on patients with cancer cachexia. J Mol Med 2010;88:85e92.

今回の研究ではカルニチン＋セレコキシブとカルニチン＋セレコキシブ＋酢酸メゲステロールで差がないことを検証する非劣性試験を行いました。その他に両群とも基本的治療としてポリフェノール、リポ酸、カルボシステイン、ビタミンE、A、Cを投与しています。治療期間は4カ月で一次アウトカムは除脂肪体重です。

結果ですが、両群で除脂肪体重の変化量に有意差を認めませんでした。例えばDEXAでは前者で2.4kg、後者で2.5kgの増加が得られています。BIAとCTでも除脂肪体重を評価していますが、両者で統計学的有意差は認めていません。歩数や身体活動に関しても統計学的有意差はありませんが、後者のほうが増えている印象です。

以上より、がん悪液質に対してカルニチン＋セレコキシブ＋酢酸メゲステロールではなく、カルニチン＋セレコキシブのみでよいという結論です。カルニチンはサプリメントとして、セレコキシブは薬剤（商品名セレコックス）として適応病名があれば臨床現場で投与可能です。悪液質に対する薬物療法の選択肢の1つになる可能性はあるかと感じています。

Abstract
BACKGROUND & AIMS: A phase III, randomized non-inferiority study was carried out to compare a two-drug combination (including nutraceuticals, i.e. antioxidants) with carnitine + celecoxib ± megestrol acetate for the treatment of cancer-related anorexia/cachexia syndrome (CACS): the primary endpoints were increase of lean body mass (LBM) and improvement of total daily physical activity. Secondary endpoint was: increase of physical performance tested by grip strength and 6-min walk test.

METHODS: Sixty eligible patients were randomly assigned to: arm 1, l-carnitine 4 g/day + Celecoxib 300 mg/day or arm 2, l-carnitine 4 g/day + celecoxib 300 mg/day + megestrol acetate 320 mg/day, all orally. All patients received as basic treatment polyphenols 300 mg/day, lipoic acid 300 mg/day, carbocysteine 2.7 g/day, Vitamin E, A, C. Treatment duration was 4 months. Planned sample size was 60 patients.

RESULTS: The results did not show a significant difference between treatment arms in both primary and secondary endpoints. Analysis of changes from baseline showed that LBM (by dual-energy X-ray absorptiometry and by L3 computed tomography) increased significantly in both arms as well as physical performance assessed by 6MWT. Toxicity was quite negligible and comparable between arms.

CONCLUSIONS: The results of the present study showed a non-inferiority of arm 1 (two-drug combination) vs arm 2 (two-drug combination + megestrol acetate). Therefore, this simple, feasible, effective, safe, low cost with favorable cost-benefit profile, two-drug approach could be suggested in the clinical practice to implement CACS treatment.