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

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1225-1233
Number of pages9
JournalCancer chemotherapy and pharmacology
Volume76
Issue number6
DOIs
Publication statusPublished - Dec 1 2015

Fingerprint

Pemetrexed
Non-Small Cell Lung Carcinoma
Cells
Maximum Tolerated Dose
Toxicity
Therapeutics
Pharmacokinetics
Chemotherapy
Safety
Liver
nintedanib
Labels
Drug-Related Side Effects and Adverse Reactions
Disease Progression
Clinical Trials
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

Cite this

Phase i study of nintedanib in combination with pemetrexed as second-line treatment of Japanese patients with advanced non-small cell lung cancer. / Daga, Haruko; Takeda, Koji; Okada, Hideaki; Miyazaki, Masaki; Ueda, Shinya; Kaneda, Hiroyasu; Okamoto, Isamu; Yoh, Kiyotaka; Goto, Koichi; Konishi, Koichi; Sarashina, Akiko; Tanaka, Tetsuya; Kaiser, Rolf; Nakagawa, Kazuhiko.

In: Cancer chemotherapy and pharmacology, Vol. 76, No. 6, 01.12.2015, p. 1225-1233.

Research output: Contribution to journalArticle

Daga, H, Takeda, K, Okada, H, Miyazaki, M, Ueda, S, Kaneda, H, Okamoto, I, Yoh, K, Goto, K, Konishi, K, Sarashina, A, Tanaka, T, Kaiser, R & Nakagawa, K 2015, 'Phase i study of nintedanib in combination with pemetrexed as second-line treatment of Japanese patients with advanced non-small cell lung cancer', Cancer chemotherapy and pharmacology, vol. 76, no. 6, pp. 1225-1233. https://doi.org/10.1007/s00280-015-2896-3
Daga, Haruko ; Takeda, Koji ; Okada, Hideaki ; Miyazaki, Masaki ; Ueda, Shinya ; Kaneda, Hiroyasu ; Okamoto, Isamu ; Yoh, Kiyotaka ; Goto, Koichi ; Konishi, Koichi ; Sarashina, Akiko ; Tanaka, Tetsuya ; Kaiser, Rolf ; Nakagawa, Kazuhiko. / Phase i study of nintedanib in combination with pemetrexed as second-line treatment of Japanese patients with advanced non-small cell lung cancer. In: Cancer chemotherapy and pharmacology. 2015 ; Vol. 76, No. 6. pp. 1225-1233.
@article{ad0f4f6b08a14978aaa90fff83bc8630,
title = "Phase i study of nintedanib in combination with pemetrexed as second-line treatment of Japanese patients with advanced non-small cell lung cancer",
abstract = "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.",
author = "Haruko Daga and Koji Takeda and Hideaki Okada and Masaki Miyazaki and Shinya Ueda and Hiroyasu Kaneda and Isamu Okamoto and Kiyotaka Yoh and Koichi Goto and Koichi Konishi and Akiko Sarashina and Tetsuya Tanaka and Rolf Kaiser and Kazuhiko Nakagawa",
year = "2015",
month = "12",
day = "1",
doi = "10.1007/s00280-015-2896-3",
language = "English",
volume = "76",
pages = "1225--1233",
journal = "Cancer Chemotherapy and Pharmacology",
issn = "0344-5704",
publisher = "Springer Verlag",
number = "6",

}

TY - JOUR

T1 - Phase i study of nintedanib in combination with pemetrexed as second-line treatment of Japanese patients with advanced non-small cell lung cancer

AU - Daga, Haruko

AU - Takeda, Koji

AU - Okada, Hideaki

AU - Miyazaki, Masaki

AU - Ueda, Shinya

AU - Kaneda, Hiroyasu

AU - Okamoto, Isamu

AU - Yoh, Kiyotaka

AU - Goto, Koichi

AU - Konishi, Koichi

AU - Sarashina, Akiko

AU - Tanaka, Tetsuya

AU - Kaiser, Rolf

AU - Nakagawa, Kazuhiko

PY - 2015/12/1

Y1 - 2015/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84947706628&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84947706628&partnerID=8YFLogxK

U2 - 10.1007/s00280-015-2896-3

DO - 10.1007/s00280-015-2896-3

M3 - Article

C2 - 26560486

AN - SCOPUS:84947706628

VL - 76

SP - 1225

EP - 1233

JO - Cancer Chemotherapy and Pharmacology

JF - Cancer Chemotherapy and Pharmacology

SN - 0344-5704

IS - 6

ER -