Phase 1 study of Gemcitabine/Nab-paclitaxel/S-1 in patients with unresectable pancreatic cancer (GeNeS1S trial)
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ORIGINAL ARTICLE
Phase 1 study of Gemcitabine/Nab‑paclitaxel/S‑1 in patients with unresectable pancreatic cancer (GeNeS1S trial) Satoshi Sai1 · Masanori Toyoda1 · Kazutoshi Tobimatsu2 · Hironaga Satake3 · Hisateru Yasui3 · Shiro Kimbara1 · Taiji Koyama1 · Yoshimi Fujishima1 · Yoshinori Imamura1 · Yohei Funakoshi1 · Naomi Kiyota1,4 · Hirochika Toyama5 · Yuzo Kodama2 · Hironobu Minami1,4 Received: 28 July 2020 / Accepted: 7 October 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Purpose We conducted a phase 1 study to determine the maximum tolerated dose and the recommended dose of gemcitabine/ nab-paclitaxel/S-1 combination chemotherapy in patients with unresectable pancreatic cancer. Methods We enrolled patients aged 20 years or older with unresectable pancreatic cancer and who had not been treated with chemotherapy or radiation therapy. Gemcitabine and nab-paclitaxel were administered on days 1 and 8, and S-1 was administered orally twice daily for 2 weeks, repeated every 3 weeks. The starting dose was level 0 [gemcitabine 700 mg/ m2, nab-paclitaxel 90 mg/m2, S-1 60/80/100 mg/day ( 1.5 m2)]. Dose-limiting toxicities were determined during the first course, and a classical 3 + 3 dose finding design was planned. Results From March 2018 to October 2019, 20 patients were enrolled. At dose level 0, three of six patients experienced dose-limiting toxicities; one grade 3 skin rash on day 8, and two grade 3 or 4 neutropenia on day 8. At dose level-1 (gemcitabine 600 mg/m2, nab-paclitaxel 90 mg/m2, and S-1 50/70/80 mg/day), two of twelve patients experienced dose-limiting toxicities, all of which were grade 3 neutropenia on day 8. The most frequently observed toxicity during eight courses was neutropenia. Other treatment-related adverse events were mild. Eleven out of 19 (58%) patients achieved partial response. Conclusion We defined the maximum tolerated dose and the recommended dose for combination therapy with gemcitabine/ nab-paclitaxel/S-1 as dose level-1. Considering the observed response rate, further studies are warranted in order to determine the efficacy of this regimen (UMIN-CTR 000030007). Keywords Unresectable pancreatic cancer · Gemcitabine · Nab-paclitaxel · S-1 · Phase 1
Introduction
* Masanori Toyoda [email protected]‑u.ac.jp 1
Department of Medical Oncology/Hematology, Kobe University Hospital and Graduate School of Medicine, 7‑5‑1 Kusunoki‑cho, Chuo‑ku, Kobe, Hyogo 650‑0017, Japan
2
Department of Gastroenterology, Kobe University Hospital and Graduate School of Medicine, Kobe, Japan
3
Department of Medical Oncology, Kobe City Hospital Organization, Kobe City Medical Center General Hospital, Kobe, Japan
4
Cancer Center, Kobe University Hospital, Kobe, Japan
5
Department of Hepato‑Biliary‑Pancreatic Surgery, Kobe University Hospital and Graduate School of Medicine, Kobe, Japan
The prognosis of patients with pancreatic cancer is one of the worst among all malignancies, with an estimated 5-year survival rate of less than 5% [1]. Many cases are diag
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