Isamu Okamoto1, Masaki Miyazaki, Masayuki Takeda, Masaaki Terashima, Koichi Azuma, Hidetoshi Hayashi, Hiroyasu Kaneda, Takayasu Kurata, Junji Tsurutani, Takashi Seto, Fumihiko Hirai, Koichi Konishi, Akiko Sarashina, Nobutaka Yagi, Rolf Kaiser, Kazuhiko Nakagawa. 1. *Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka, Japan; †Center for Clinical and Translational Research, Faculty of Medicine, Kyusyu University Hospital, Fukuoka, Japan; ‡Department of Internal Medicine, Suita Municipal Hospital, Osaka, Japan; §Department of Medical Oncology, Nara Hospital, Kinki University Faculty of Medicine, Nara, Japan; ║Department of Medicine, Division of Respirology, Neurology, and Rheumatology, Kurume University Hospital, Fukuoka, Japan; ¶Department of Medical Oncology, Kishiwada Municipal Hospital, Osaka, Japan; #Department of Thoracic Oncology, Kansai Medical University, Hirakata Hospital, Osaka, Japan; **Department of Medical Oncology, National Kyushu Cancer Centre, Fukuoka, Japan; ††Department of Medical Oncology, National Kyushu Cancer Centre, Fukuoka, Japan; ‡‡Nippon Boehringer Ingelheim Co. Ltd., Medical Development Division, Hyogo, Japan; and §§Clinical Pharmacokinetics/Pharmacodynamics Department, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
Abstract
BACKGROUND: This phase I, open-label study evaluated the safety/tolerability and maximum tolerated dose of second-line nintedanib combined with docetaxel in Japanese patients with advanced non-small-cell lung cancer. METHODS: Eligible patients received docetaxel 60 or 75 mg/m(2) (day 1) plus nintedanib 100, 150, or 200 mg twice daily (bid; days 2-21) in 21-day cycles. Standard 3 + 3 dose escalations were performed separately in patient cohorts with a body surface area (BSA) of less than 1.5 m(2) (BSA <1.5) and BSA greater than or equal to 1.5, respectively. RESULTS: Forty-two patients (17 BSA <1.5, 25 BSA ≥ 1.5) were treated. The maximum tolerated dose of nintedanib was 150 and 200 mg bid in patients with BSA less than 1.5 and BSA greater than or equal to 1.5 (BSA ≥ 1.5), respectively, in combination with 75 mg/m(2) of docetaxel. Dose-limiting toxicities (all grade 3 hepatic enzyme elevations) occurred in 12 patients (six per cohort). Drug-related adverse events included neutropenia (95%), leukopenia (83%), fatigue (76%), alopecia (71%), decreased appetite (67%), and elevations in alanine aminotransferase (64%) and aspartate aminotransferase (64%). All hepatic enzyme elevations were reversible and manageable with dose reduction or discontinuation. Among 38 evaluable patients, 10 (26%) had a partial response and 18 (47%) had stable disease. CONCLUSION: Continuous treatment with second-line nintedanib combined with docetaxel was manageable and showed promising signs of efficacy in Japanese patients with advanced non-small-cell lung cancer.
BACKGROUND: This phase I, open-label study evaluated the safety/tolerability and maximum tolerated dose of second-line nintedanib combined with docetaxel in Japanese patients with advanced non-small-cell lung cancer. METHODS: Eligible patients received docetaxel 60 or 75 mg/m(2) (day 1) plus nintedanib 100, 150, or 200 mg twice daily (bid; days 2-21) in 21-day cycles. Standard 3 + 3 dose escalations were performed separately in patient cohorts with a body surface area (BSA) of less than 1.5 m(2) (BSA <1.5) and BSA greater than or equal to 1.5, respectively. RESULTS: Forty-two patients (17 BSA <1.5, 25 BSA ≥ 1.5) were treated. The maximum tolerated dose of nintedanib was 150 and 200 mg bid in patients with BSA less than 1.5 and BSA greater than or equal to 1.5 (BSA ≥ 1.5), respectively, in combination with 75 mg/m(2) of docetaxel. Dose-limiting toxicities (all grade 3 hepatic enzyme elevations) occurred in 12 patients (six per cohort). Drug-related adverse events included neutropenia (95%), leukopenia (83%), fatigue (76%), alopecia (71%), decreased appetite (67%), and elevations in alanine aminotransferase (64%) and aspartate aminotransferase (64%). All hepatic enzyme elevations were reversible and manageable with dose reduction or discontinuation. Among 38 evaluable patients, 10 (26%) had a partial response and 18 (47%) had stable disease. CONCLUSION: Continuous treatment with second-line nintedanib combined with docetaxel was manageable and showed promising signs of efficacy in Japanese patients with advanced non-small-cell lung cancer.
Authors: C H Chung; V B Guthrie; D L Masica; C Tokheim; H Kang; J Richmon; N Agrawal; C Fakhry; H Quon; R M Subramaniam; Z Zuo; T Seiwert; Z R Chalmers; G M Frampton; S M Ali; R Yelensky; P J Stephens; V A Miller; R Karchin; J A Bishop Journal: Ann Oncol Date: 2015-02-23 Impact factor: 32.976