婦人科がんの悪液質に対する複合療法

婦人科がん患者の悪液質に対する複合療法のphase III RCTを紹介します。

Macciò A, Madeddu C, Gramignano G, Mulas C, Floris C, Sanna E, Cau MC, Panzone F, Mantovani G. A randomized phase III clinical trial of a combined treatment for cachexia in patients with gynecological cancers: Evaluating the impact on metabolic and inflammatory profiles and quality of life. Gynecol Oncol. 2011 Dec 20. [Epub ahead of print]

抄録しか読んでいませんので、詳細はわかりませんが、PECOにすると以下のようになります。

P：悪液質の婦人科がん患者104人（子宮がんか卵巣がんでしょう）に
E：酢酸メゲストロール（黄体ホルモン製剤）＋Lカルニチン＋セレコキシブ（COX-2 選択的阻害剤の非ステロイド性消炎鎮痛薬）＋抗酸化物質（詳細不明）を投与すると、
C：酢酸メゲストロールのみを投与する場合と比較して
O：除脂肪体重、安静時エネルギー消費量、疲労、QOLがよい

結果ですが、介入群のほうが除脂肪体重、安静時エネルギー消費量、疲労、QOLとも、よりよかったです。二次アウトカムとして、IL-6, TNF-α, CRP、活性酸素も介入群のみ減少しました。

Lカルニチン、セレコキシブ、抗酸化物質のどれがよかったのかは不明ですが、悪液質の場合、これらの複合療法が悪液質改善に有効な可能性があるといえます。

Abstract
OBJECTIVES: Gynecological neoplastic disease progression is characterized by specific energy metabolism alterations and by symptoms including fatigue, anorexia, nausea, anemia, and immunodepression, which result in a cachexia syndrome and a marked decrease in patient quality of life (QoL). Therapeutic protocols associated with appropriate and effective psychological and social support systems are essential to counteract the symptoms of neoplastic disease in incurable patients.

METHODS: A phase III randomized study was performed to establish the most effective and safest treatment to improve the key symptoms in advanced gynecological cancer patients, i.e., lean body mass (LBM), resting energy expenditure (REE), fatigue, and QoL. In addition, the impact of the treatment arms on the main metabolic and inflammatory parameters, including C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α, leptin, reactive oxygen species (ROS), and glutathione peroxidase, was evaluated. The change in the Glasgow Prognostic Score (GPS) during treatment was also assessed. A total of 104 advanced-stage gynecological cancer patients were enrolled and randomly assigned to receive either megestrol acetate (MA) plus l-carnitine, celecoxib, and antioxidants (arm 1) or MA alone (arm 2). The treatment duration was 4months.

RESULTS: The combination arm was more effective than arm 2 with respect to LBM, REE, fatigue, and global QoL. As for the secondary efficacy endpoints, patient appetite increased, and ECOG PS decreased significantly in both arms. The inflammation and oxidative stress parameters IL-6, TNF-α, CRP, and ROS decreased significantly in arm 1, while no significant change was observed in arm 2.

CONCLUSIONS: The combined treatment improved both immunometabolic alterations and patient QoL. Multimodality therapies for cachexia ideally should be introduced within a context of "best supportive care" that includes optimal symptom management and careful psychosocial counseling.