Phase i study of nintedanib in combination with pemetrexed as second-line treatment of Japanese patients with advanced non-small cell lung cancer

Haruko Daga, Koji Takeda, Hideaki Okada, Masaki Miyazaki, Shinya Ueda, Hiroyasu Kaneda, Isamu Okamoto, Kiyotaka Yoh, Koichi Goto, Koichi Konishi, Akiko Sarashina, Tetsuya Tanaka, Rolf Kaiser, Kazuhiko Nakagawa

研究成果: Contribution to journalArticle査読

5 被引用数 (Scopus)

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Purpose: This open-label, phase I, dose-escalation part of a phase I/II study evaluated the safety, pharmacokinetics, and preliminary efficacy of nintedanib, a triple angiokinase inhibitor, combined with pemetrexed in Japanese patients with advanced non-small cell lung cancer (NSCLC) after first-line chemotherapy. Methods: A fixed dose of pemetrexed (500 mg/m2 iv) was administered on Day 1 of each 21-day cycle followed by oral nintedanib twice daily (bid) on days 2-21, starting at 100 mg bid and escalating to 200 mg bid in 50-mg intervals, using a standard 3 + 3 design. After ≥4 cycles of combination therapy, patients could continue nintedanib monotherapy until disease progression or undue adverse events (AEs). Primary endpoints were maximum tolerated dose (MTD), defined as the highest dose at which the incidence of dose-limiting toxicities (DLTs) was <33.3 % during the first treatment course, and AEs (CTCAE v3.0). DLTs were primarily defined as grade ≥3 non-hematologic or grade 4 hematologic AEs. Results: Eighteen patients were included in the analysis. DLTs were experienced by 2/9 patients receiving 200 mg bid, 1/6 receiving 150 mg bid, and 0/3 receiving the lowest dose. The MTD of nintedanib plus pemetrexed was 200 mg bid. The most common drug-related AEs were elevated liver enzymes and gastrointestinal AEs. Two patients achieved partial response, and 10 had stable disease. Conclusions: Nintedanib plus pemetrexed had a manageable safety profile and showed promising signs of efficacy in previously treated Japanese patients with advanced NSCLC. As in Caucasian patients, the MTD of nintedanib was 200 mg bid. Clinical trial information NCT00979576.

本文言語英語
ページ(範囲)1225-1233
ページ数9
ジャーナルCancer chemotherapy and pharmacology
76
6
DOI
出版ステータス出版済み - 12 1 2015

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 毒物学
  • 薬理学
  • 癌研究
  • 薬理学(医学)

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