title: Tolerability of nintedanib (BIBF 1120) in combination with docetaxel: a phase 1 study in Japanese patients with previously treated non-small-cell lung cancer.
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.
  
  
  CONCLUSIONS
  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.affiliation: *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.
authors.forename: Isamu
authors.initials: I
authors.lastname: Okamoto
authors.forename: Masaki
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takeda
authors.forename: Masaaki
authors.initials: M
authors.lastname: Terashima
authors.forename: Koichi
authors.initials: K
authors.lastname: Azuma
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Hayashi
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Kaneda
authors.forename: Takayasu
authors.initials: T
authors.lastname: Kurata
authors.forename: Junji
authors.initials: J
authors.lastname: Tsurutani
authors.forename: Takashi
authors.initials: T
authors.lastname: Seto
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Hirai
authors.forename: Koichi
authors.initials: K
authors.lastname: Konishi
authors.forename: Akiko
authors.initials: A
authors.lastname: Sarashina
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Yagi
authors.forename: Rolf
authors.initials: R
authors.lastname: Kaiser
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D000077143:Docetaxel; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects; D007564:Japan; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D007211:Indoles; D043823:Taxoids; D000077143:Docetaxel; C530716:nintedanib