Tolerability of nintedanib (BIBF 1120) in combination with docetaxel

A phase 1 study in japanese patients with previously treated non-small-cell lung cancer

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

Research output: Contribution to journalArticle

26 Citations (Scopus)

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 (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 (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 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.

Original languageEnglish
Pages (from-to)346-352
Number of pages7
JournalJournal of Thoracic Oncology
Volume10
Issue number2
DOIs
Publication statusPublished - Feb 6 2015

Fingerprint

docetaxel
Body Surface Area
Non-Small Cell Lung Carcinoma
Maximum Tolerated Dose
nintedanib
Liver
Alopecia
Leukopenia
Appetite
Enzymes
Aspartate Aminotransferases
Neutropenia
Drug-Related Side Effects and Adverse Reactions
Alanine Transaminase
Fatigue

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Tolerability of nintedanib (BIBF 1120) in combination with docetaxel : A phase 1 study in japanese patients with previously treated non-small-cell lung cancer. / Okamoto, Isamu; Miyazaki, Masaki; Takeda, Masayuki; Terashima, Masaaki; Azuma, Koichi; Hayashi, Hidetoshi; Kaneda, Hiroyasu; Kurata, Takayasu; Tsurutani, Junji; Seto, Takashi; Hirai, Fumihiko; Konishi, Koichi; Sarashina, Akiko; Yagi, Nobutaka; Kaiser, Rolf; Nakagawa, Kazuhiko.

In: Journal of Thoracic Oncology, Vol. 10, No. 2, 06.02.2015, p. 346-352.

Research output: Contribution to journalArticle

Okamoto, I, Miyazaki, M, Takeda, M, Terashima, M, Azuma, K, Hayashi, H, Kaneda, H, Kurata, T, Tsurutani, J, Seto, T, Hirai, F, Konishi, K, Sarashina, A, Yagi, N, Kaiser, R & Nakagawa, K 2015, 'Tolerability of nintedanib (BIBF 1120) in combination with docetaxel: A phase 1 study in japanese patients with previously treated non-small-cell lung cancer', Journal of Thoracic Oncology, vol. 10, no. 2, pp. 346-352. https://doi.org/10.1097/JTO.0000000000000395
Okamoto, Isamu ; Miyazaki, Masaki ; Takeda, Masayuki ; Terashima, Masaaki ; Azuma, Koichi ; Hayashi, Hidetoshi ; Kaneda, Hiroyasu ; Kurata, Takayasu ; Tsurutani, Junji ; Seto, Takashi ; Hirai, Fumihiko ; Konishi, Koichi ; Sarashina, Akiko ; Yagi, Nobutaka ; Kaiser, Rolf ; Nakagawa, Kazuhiko. / Tolerability of nintedanib (BIBF 1120) in combination with docetaxel : A phase 1 study in japanese patients with previously treated non-small-cell lung cancer. In: Journal of Thoracic Oncology. 2015 ; Vol. 10, No. 2. pp. 346-352.
@article{3b8ab6e5435b422e8095c475a00d3b80,
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 (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 (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 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.",
author = "Isamu Okamoto and Masaki Miyazaki and Masayuki Takeda and Masaaki Terashima and Koichi Azuma and Hidetoshi Hayashi and Hiroyasu Kaneda and Takayasu Kurata and Junji Tsurutani and Takashi Seto and Fumihiko Hirai and Koichi Konishi and Akiko Sarashina and Nobutaka Yagi and Rolf Kaiser and Kazuhiko Nakagawa",
year = "2015",
month = "2",
day = "6",
doi = "10.1097/JTO.0000000000000395",
language = "English",
volume = "10",
pages = "346--352",
journal = "Journal of Thoracic Oncology",
issn = "1556-0864",
publisher = "International Association for the Study of Lung Cancer",
number = "2",

}

TY - JOUR

T1 - Tolerability of nintedanib (BIBF 1120) in combination with docetaxel

T2 - A phase 1 study in japanese patients with previously treated non-small-cell lung cancer

AU - Okamoto, Isamu

AU - Miyazaki, Masaki

AU - Takeda, Masayuki

AU - Terashima, Masaaki

AU - Azuma, Koichi

AU - Hayashi, Hidetoshi

AU - Kaneda, Hiroyasu

AU - Kurata, Takayasu

AU - Tsurutani, Junji

AU - Seto, Takashi

AU - Hirai, Fumihiko

AU - Konishi, Koichi

AU - Sarashina, Akiko

AU - Yagi, Nobutaka

AU - Kaiser, Rolf

AU - Nakagawa, Kazuhiko

PY - 2015/2/6

Y1 - 2015/2/6

N2 - 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 (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 (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 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.

AB - 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 (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 (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 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.

UR - http://www.scopus.com/inward/record.url?scp=84922221042&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84922221042&partnerID=8YFLogxK

U2 - 10.1097/JTO.0000000000000395

DO - 10.1097/JTO.0000000000000395

M3 - Article

VL - 10

SP - 346

EP - 352

JO - Journal of Thoracic Oncology

JF - Journal of Thoracic Oncology

SN - 1556-0864

IS - 2

ER -