ERCC1高発現進行非小細胞肺癌に対する非白金３剤併用療法の第Ⅱ相試験

Background: We prospectively evaluated the efficacy and toxicity of a non-platinum triplet regimen for patients with advanced non-small cell lung cancer (NSCLC) expected to be platinum-resistant. Methods: Patients were diagnosed with NSCLC using endobronchial ultrasonography with a guide sheath as a core biopsy. RNA was immediately isolated from unfixed biopsy specimens, and quantitative real-time reverse transcription-PCR assays were performed to determine ERCC1 messenger RNA expression. Patients with advanced, untreated NSCLC showing high ERCC1 levels (ΔCt ≧ 6.5) were assigned a non-platinum triplet regimen of irinotecan and paclitaxel plus bevacizumab. The primary end point was the objective response rate (ORR). Results: A total of 141 untreated patients were evaluated and 30 patients were entered into this phase II trial. The ORR was 66.7% (95% confidence interval [CI] 47.2?82.7) and median progression-free survival (PFS) was 215 days. Grade 4 thrombosis occurred in one patient, but other toxicities were mild and controllable. Fifty-six patients were treated with platinum-containing regimens and 24 patients responded (ORR 42.8%, 95% CI 29.7?56.7). Twenty-nine of these patients had high ERCC1 levels, of which 6 patients responded; 27 patients had low ERCC1 levels, 18 patients responded (P = 0.0053 by Fisher’s exact test). Conclusion: The triplet combination might be effective for patients with advanced, untreated NSCLC overexpressing ERCC1. ERCC1 messenger RNA levels may be a predictive factor for response to platinum-containing regimens.長崎大学学位論文 学位記番号:博(医歯薬)甲第1166号 学位授与年月日:令和元年6月5日Author: Shinnosuke Takemoto, Yoichi Nakamura, Hiroshi Gyoutoku, Hiroaki Senju, Daiki Ogawara, Takaya Ikeda, Hiroyuki Yamaguchi, Takeshi Kitazaki, Hirofumi Nakano, Katsumi Nakatomi, Shinya Tomari, Shuntaro Sato, Seiji Nagashima, Minoru Fukuda, Hiroshi MukaeCitation: Thoracic Cancer, 10(3), pp.452-458 ; 2019Nagasaki University (長崎大学)課程博