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Phase I/II Study of S-1 Plus Cisplatin Alternating With S-1 Plus Docetaxel in Patients With Advanced Gastric Cancer

Hosokawa, Ayumu, MD, PhD*; Ando, Takayuki, MD, PhD*; Ogawa, Kohei, MD, PhD*; Ueda, Akira, MD, PhD*; Yoshita, Hiroki, MD, PhD*; Mihara, Hiroshi, MD, PhD*; Fujinami, Haruka, MD, PhD*; Kajiura, Shinya, MD, PhD*; Yabushita, Kazuhisa, MD, PhD; Horikawa, Naoki, MD, PhD; Kobayashi, Yuka, MD; Yoshioka, Akira, MD, PhD§; Origasa, Hideki, PhD; Sugiyama, Toshiro, MD, PhD*

American Journal of Clinical Oncology: October 2018 - Volume 41 - Issue 10 - p 977–981
doi: 10.1097/COC.0000000000000405
Original Articles: Gastrointestinal

Objectives: To investigate the usefulness of S-1 plus cisplatin alternating with S-1 plus docetaxel as first-line treatment in patients with advanced gastric cancer, we conducted a phase I/II study to determine the maximum tolerated dose and recommended dose, and evaluate efficacy and toxicity.

Materials and Methods: Patients with histologically confirmed unresectable and recurrent gastric cancer were enrolled in this study. Cisplatin was administered on day 1 and the dose escalated by 10 mg/m2 from a starting dose of 40 mg/m2 in the phase I part. S-1 was given orally at 80 mg/m2 on days 1 to 14 and docetaxel at 40 mg/m2 on day 22 in combination with S-1 80 mg/m2 on days 22 to 35. The treatment was repeated every 6 weeks. The primary endpoint of the phase II analysis was the response rate.

Results: Nine patients entered the phase I and 24 the phase II part. Because 50% of patients (3/6) developed dose-limiting toxicities in the phase I part, the maximum tolerated dose of cisplatin was presumed to be 50 mg/m2. Therefore, the estimated recommended dose of cisplatin was 40 mg/m2; 27 patients received that dose. The response rate was 59.3% (95% confidence interval, 40.8-77.8) and the median follow-up 26.2 months. The median progression-free survival was 7.9 months and the median overall survival 18.6 months. The most common grade 3/4 toxicities were neutropenia (59.3%), leucopenia (37.0%), and anemia (29.6%). These toxicities were tolerable and manageable.

Conclusion: This alternating treatment seems to have promising activity with tolerable toxicities in the first-line treatment of patients with advanced gastric cancer.

*Department of Gastroenterology and Hematology, Faculty of Medicine, University of Toyama

Department of Surgery, Takaoka City Hospital, Takaoka

Division of Biostatistics and Clinical Epidemiology, University of Toyama, Toyama

Department of Gastroenterology, Tachikawa General Hospital, Nagaoka, Niigata

§Department of Oncology, Mitsubishi Kyoto Hospital, Kyoto, Japan

A.H. received honoraria from Chugai Pharma, Taiho Pharmaceutical, Yakult Honsha, Takeda, Tsumura, Bayer, Eisai, and Bristol-Myers Squibb. A.H.’s institution received research funding from Chugai Pharma, Taiho Pharmaceutical, and Daiichi Sankyo. K.Y. received honoraria from Chugai Pharma, Kaken Pharmaceutical, Asahi Kasei Pharma, Yakult Honsha, and Taiho Pharmaceutical. N.H. received honoraria from Taiho Pharmaceutical. Y.K. received honoraria from Chugai Pharma, Taiho Pharmaceutical, Takeda, Bristol-Myers Squibb, Eli Lilly, and Merck Serono. A.Y. received honoraria from Bayer, Hisamitsu Pharmaceutical, Taiho Pharmaceutical, MSD, Eli Lilly, Takeda, Merck Serono, and Chugai Pharma. T.S. received honoraria from Takeda, AstraZeneca, Eisai, Pfizer, Daiichi Sankyo, and Otsuka. He received a research grant from Ministry of Health, Labour and Welfare, Japan. His institution received research funding from Takeda, AstraZeneca, Eisai, Pfizer, Novartis, Bayer, Daiichi Sankyo, and Otsuka. The remaining authors declare no conflicts of interest.

Reprints: Ayumu Hosokawa, MD, PhD, Department of Gastroenterology and Hematology, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama, Toyama 930-0194, Japan. E-mail:

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