期刊
CANCER CHEMOTHERAPY AND PHARMACOLOGY
卷 79, 期 6, 页码 1169-1177出版社
SPRINGER
DOI: 10.1007/s00280-017-3313-x
关键词
Galunisertib; Gemcitabine; Japanese; Pancreatic cancer; Pharmacokinetics; Phase 1b; Safety
资金
- Eli Lilly Japan [LY2157299, H9H-JE-JBAO]
- Eli Lilly and Company
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/m(2) 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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