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.

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: Isamu Okamoto, 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
• Journal: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (J Thorac Oncol) Vol. 10 Issue 2 Pg. 346-52 (Feb 2015) ISSN: 1556-1380 [Electronic] United States
• PMID: 25299232 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Indoles
• Taxoids
• Docetaxel
• nintedanib

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Docetaxel
• Female
• Humans
• Indoles (administration & dosage, adverse effects)
• Japan
• Lung Neoplasms (drug therapy)
• Male
• Middle Aged
• Taxoids (administration & dosage, adverse effects)