© The Author (2008). Published by Oxford University Press. All rights reserved
A Phase I Study of Combination Therapy of the Oral Fluorinated Pyrimidine Compound S-1 with Low-dose Cisplatin Twice-a-week Administration (JFMC27-9902 Step2) in Patients with Advanced Gastric Cancer Using a Continual Reassessment Method
1 Program in Health and Community Medicine, Nagoya University Graduate School of Medicine, Nagoya
2 Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka
3 Department of Clinical Oncology, Kochi Health Sciences Center, Kochi
4 Department of Clinical Oncology, Tohoku Employees' Pension Welfare Hospital, Sendai
5 Kitasato Institute for Life Sciences, Kitasato University
6 Japanese Foundation for Multidisciplinary Treatment of Cancer, Tokyo,
7 Department of Biostatistics/Epidemiology and Preventive Health Sciences, School of Health Sciences and Nursing, University of Tokyo, Tokyo, Japan
For reprints and all correspondence: Satoshi Morita, Program in Health and Community Medicine, Nagoya University Graduate School of Medicine, 65 Tsuruma-Cho, Showa-Ku, Nagoya 466-8550, Japan. E-mail: smorita{at}med.nagoya-u.ac.jp
Received June 19, 2007; accepted August 17, 2007
Objective: We conducted a Phase I study to evaluate the safety and efficacy of a combination of S-1 with semi-weekly low-dose cisplatin in patients with unresectable/recurrent gastric cancer to determine the recommended dose (RD) for a subsequent Phase II study.
Methods: S-1 was administered orally at 80–120 mg/body/day based on body surface area. One cycle consisted of the consecutive administration of S-1 for 28 days followed by 14 days rest. Three dose levels, 7.5, 10, and 15 mg/m2/day, were set for cisplatin, which was administered twice-a-week for 4 weeks followed by 2 weeks of rest in each cycle. Dose-limiting toxicity (DLT) data were continually monitored to enable decisions regarding cisplatin dose escalation and deescalation based on a new dose-finding algorithm using a continual reassessment method (CRM). The CRM target toxicity level to estimate the RD was set at 20%.
Results: Eight and five patients were treated at cisplatin dose levels of 10 and 15 mg/m2/day, respectively. Two DLTs occurred at both dose levels. On the basis of this data, the CRM estimated the RD to be 10 mg/m2/day of cisplatin. Three patients of eight patients treated with 10 mg/m2/day of cisplatin exhibited a confirmed partial response during the treatment period.
Conclusion: For future trials examining the safety and efficacy of daily S-1 with semi-weekly cisplatin in patients with unresectable/recurrent gastric cancer, we found a cisplatin RD of 10 mg/m2/day.
Key Words: S-1 • low-dose cisplatin • continual reassessment method • gastric cancer • Phase I clinical study