Phase I/II study of nab-paclitaxel plus gemcitabine for chemotherapy-naive Japanese patients with metastatic pancreatic cancer
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Efficacy and safety of nab-paclitaxel plus gemcitabine have not been clarified in Japanese patients with metastatic pancreatic cancer. No pharmacokinetic profile of co-administration of nab-paclitaxel and gemcitabine has been reported. We conducted a phase I/II study of the efficacy, safety, and pharmacokinetics in Japanese patients with metastatic pancreatic cancer.
The patients were administered 125 mg/m2 nab-paclitaxel followed by 1000 mg/m2 gemcitabine on day 1, 8, and 15 every 4 weeks. Treatment was continued until disease progression, unacceptable adverse events, or withdrawal of consent, whichever occurred first. The primary endpoints were tolerability in phase I and overall response rate according to RECIST in phase II.
A total of 34 patients were enrolled. At the time of 1-year follow-up analysis since the last patient enrollment, the objective response rate by independent review committee was 58.8 % (20 of 34 patients; 95 % confidence interval [CI], 40.7–75.4 %). The median progression-free survival and median overall survival were 6.5 months (95 % CI, 5.1–8.3) and 13.5 months (95 % CI, 10.6—not reached), respectively. Main adverse drug reactions of grade 3 or higher were neutropenia (70.6 %), leukopenia (55.9 %), anemia (14.7 %), lymphocytopenia (14.7 %), thrombocytopenia (14.7 %), and peripheral sensory neuropathy (11.8 %). There were no treatment-related deaths and no marked differences in pharmacokinetics of combined paclitaxel and gemcitabine in historical comparison between co-administration and monotherapies.
Nab-paclitaxel plus gemcitabine regimen showed highly promising efficacy with manageable safety profile under careful observation and with appropriate supportive care in Japanese patients with metastatic pancreatic cancer.
Clinical trial number
KeywordsCombination chemotherapy Gemcitabine Nab-paclitaxel Pancreatic cancer Pharmacokinetics
We thank all of the participating patients and their families, as well as the investigators and clinical research coordinators. We are grateful to Yutaka Ariyoshi, Yusuke Tanigawara, and Keisuke Aiba, who served as members of the Data and Safety Monitoring Committee, and Atsushi Sato and Kouki Yoshikawa as members of the Independent Review Committee.
This study was funded by Taiho Pharmaceutical Co., Ltd.
Compliance with ethical standards
Conflict of interest
The study was designed under the responsibility of Taiho Pharmaceutical. Study drug was provided by Taiho Pharmaceutical. In collaboration with all authors, Taiho Pharmaceutical designed the study, analyzed and interpreted the data, and edited the report. Data were recorded at participating clinical centers and maintained by Taiho Pharmaceutical. All authors had full access to all of the data in the study and had final responsibility for the decision to submit for publication. We also thank to Takanori Tanase for his contribution as biostatistician, Taiho Pharmaceutical, for overall management of the trial and drafting the manuscript. Hideki Ueno received honoraria from Taiho Pharmaceutical; he has also received research funding from Taiho Pharmaceutical, OncoTherapy Science, Eli Lilly Japan, Merck Serono Japan, and Zeria Pharmaceutical. Masafumi Ikeda received honoraria from Taiho Pharmaceutical, Bayer Yakuhin, Bristol Myers, Abbott Japan, Yakult Honsha, and Novartis Pharmaceutical; he has also received research funding from Taiho Pharmaceutical, Bayer Yakuhin, Merck Serono, Kyowa Hakko Kirin, Yakult Honsha, Eli Lilly Japan, Chugai Pharmaceutical, OncoTherapy Science, Boehringer Ingelheim, Kowa, Ono Pharmaceutical, Eisai, AstraZeneca, Glaxo Smithkline, Pfizer Japan, Takeda Pharmaceutical, and Zeria Pharmaceutical. Makoto Ueno received honoraria from Taiho Pharmaceutical; he has also received research funding from Taiho Pharmaceutical, Merck Serono, and Zeria Pharmaceutical. Nobumasa Mizuno received research funding from Taiho Pharmaceutical, Merck Serono, AstraZeneca, Zeria Pharmaceutical, and Takeda Pharmaceutical. Tatsuya Ioka received honoraria from Taiho Pharmaceutical and Chugai Pharmaceutical; he has also receibved research funding from Taiho Pharmaceutical, Merck Serono, AstraZeneca, Zeria Pharmaceutical, Nippon Zoki Pharmaceutical, Yakult Honsha, and Glaxo Smithkline. Yasushi Omuro received research funding from Taiho Pharmaceutical, MSD, Ono Pharmaceutical, Eli Lilly Japan, Chugai Pharmaceutical, and Merck Serono. Takako E Nakajima received honoraria from Taiho Pharmaceutical; she has also received research funding from Taiho Pharmaceutical and Eli Lilly Japan. Junji Furuse received honoraria from Taiho Pharmaceutical, Chugai Pharmaceutical, Bayer Yakuhin, Eisai, Ono Pharmaceutical, Zeria Pharmaceutical, Eli Lilly Japan, Boehringer Ingelheim, Novartis Pharmaceutical, Kyowa Hakko Kirin, Yakult Honsha, Merck Serono, and FUJIFILM Corporation; he has also received research funding from Taiho Pharmaceutical, Ono Pharmaceutical, OncoTherapy Science, Bayer Yakuhin, Eli Lilly Japan, Chugai Pharmaceutical, Glaxo Smithkline, Takeda Pharmaceutical, Zeria Pharmaceutical, and Merck Serono.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
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