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Erschienen in: Cancer Chemotherapy and Pharmacology 6/2017

27.04.2017 | Original Article

Phase 1b study of galunisertib in combination with gemcitabine in Japanese patients with metastatic or locally advanced pancreatic cancer

verfasst von: Masafumi Ikeda, Hideaki Takahashi, Shunsuke Kondo, Michael Mauritius Fabio Lahn, Ken Ogasawara, Karim A. Benhadji, Hisaki Fujii, Hideki Ueno

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 6/2017

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Abstract

Purpose

Transforming growth factor-beta inhibitors may enhance the antitumor activity of gemcitabine with acceptable safety and tolerability. This open-label, multicenter, non-randomized phase 1b study assessed the safety/tolerability, pharmacokinetics, and tumor response of galunisertib plus gemcitabine in Japanese patients with advanced or metastatic pancreatic cancer.

Methods

During each 28-day cycle, galunisertib 150 mg was administered orally twice daily (300 mg/day) for 14 days, followed by 14 days of rest. Gemcitabine 1000 mg/m2 was intravenously given on Days 8, 15, and 22. Safety was assessed by the incidence of dose-limiting toxicities (DLTs) in the first cycle and treatment-emergent adverse events (TEAEs). Efficacy was assessed by antitumor activity and changes in carbohydrate antigen 19-9 (CA19-9).

Results

No DLTs were reported. All 7 enrolled patients had ≥1 TEAE, of which the most common included anorexia, decreased neutrophil count, and decreased white blood cell count. Grade ≥3 TEAEs were observed in 6 patients; 4 patients had Grade ≥3 TEAEs (decreased neutrophil, white blood cell, and lymphocyte count; hypophosphatemia) considered possibly related to study drug(s). The pharmacokinetic profile of galunisertib in combination with gemcitabine was similar to that previously observed for galunisertib alone. The clinical response [complete response (CR), partial response (PR), or stable disease] rate was 42.9%, and the median progression-free survival was 64 days; no CR/PR were achieved.

Conclusion

Galunisertib plus gemcitabine had an acceptable safety/tolerability profile with evidence of efficacy in Japanese patients with advanced or metastatic pancreatic cancer.
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Metadaten
Titel
Phase 1b study of galunisertib in combination with gemcitabine in Japanese patients with metastatic or locally advanced pancreatic cancer
verfasst von
Masafumi Ikeda
Hideaki Takahashi
Shunsuke Kondo
Michael Mauritius Fabio Lahn
Ken Ogasawara
Karim A. Benhadji
Hisaki Fujii
Hideki Ueno
Publikationsdatum
27.04.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Chemotherapy and Pharmacology / Ausgabe 6/2017
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-017-3313-x

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