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Phase II trial of a non‐platinum triplet for patients with advanced non‐small cell lung carcinoma (NSCLC) overexpressing ERCC1 messenger RNA

Authors :
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 Mukae
Source :
Thoracic Cancer, Vol 10, Iss 3, Pp 452-458 (2019)
Publication Year :
2019
Publisher :
Wiley, 2019.

Abstract

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.

Details

Language :
English
ISSN :
17597714 and 17597706
Volume :
10
Issue :
3
Database :
Directory of Open Access Journals
Journal :
Thoracic Cancer
Publication Type :
Academic Journal
Accession number :
edsdoj.2b3fae3714c2483aa51b824458e6380a
Document Type :
article
Full Text :
https://doi.org/10.1111/1759-7714.12958