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Phase I/II study of 3-week combination of S-1 and cisplatin chemotherapy for metastatic or recurrent gastric cancer

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Abstract

Purpose

To define the maximum-tolerated dose (MTD) of S-1, given daily for 2 weeks followed by a 1-week rest, with a fixed dose of cisplatin on the initial day, and to determine the activity and safety of this regimen at the recommended dose (RD) when used as first line treatment of advanced gastric cancer (AGC).

Patients and methods

Cisplatin was fixed at a dose of 60 mg/m2 on day 1 (D1) and the starting dose of S-1 was 60 mg/m2/day (30 mg/m2 bid) (level I) on D1 to D14, every 3 weeks. The dose of S-1 was increased by 5 mg/m2 bid up to 100 mg/m2/day (level V) unless the MTD was achieved.

Results

Sixty-two eligible patients were enrolled. MTD was set at level V with two of three patients developing grade 3 diarrhea or febrile neutropenia. The RD was determined at level IV (90 mg/m2/day). After the first 20 patients were enrolled in phase II, the protocol was amended; the S-1 dose was reduced to 80 mg/m2/day (N = 23) because of poor bone marrow recovery. The objective response was observed in 20 of 42 evaluable patients (48%). SD was achieved in 15 (36%). The median PFS was 5.3 months (95% CI, 4.6–6.0 months) with a median OS of 10.0 months (95% CI, 5.1–14.8 months). Grade 3–4 toxicities included neutropenia (33%), anemia (31%), and anorexia (24%).

Conclusions

The 3-week combination of cisplatin plus S-1 is active against AGC with favorable toxicitiy profiles. The phase II schedule or doses may need further refinements.

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Acknowledgment

This study was supported in part by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (A060775). S-1 was provided by Jeil Pharmacetucial Co. Ltd. Seoul, Korea. This study was presented in part at the 2007 ASCO Gastrointestinal Cancer Symposium, Orlando, Fl, USA., January 19–21, 2007. The authors are indebted to Professor J. Patrick Barron of the International Medical Communications Center of Tokyo Medical University and Professor Jaffer A. Ajani of the University of Texas M. D. Anderson Cancer Center for their review of this manuscript.

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Authors and Affiliations

  1. Division of Oncology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap-dong, Songpa-gu, Seoul, 138-736, South Korea

    Jae-Lyun Lee, Hye Jin Kang, Yoon-Koo Kang, Min-Hee Ryu, Heung Moon Chang, Tae-Won Kim, Hee Jung Sohn, Hawk Kim & Jung Shin Lee

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  1. Jae-Lyun Lee
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Correspondence to Yoon-Koo Kang.

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Lee, JL., Kang, H.J., Kang, YK. et al. Phase I/II study of 3-week combination of S-1 and cisplatin chemotherapy for metastatic or recurrent gastric cancer. Cancer Chemother Pharmacol 61, 837–845 (2008). https://doi.org/10.1007/s00280-007-0541-5

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  • DOI: https://doi.org/10.1007/s00280-007-0541-5

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