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Phase I/II and pharmacokinetic study of S-1 and oxaliplatin in previously untreated advanced gastric cancer

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Abstract

Background

We aimed to determine the maximum-tolerated dose (MTD) of S-1 when given with oxaliplatin, to evaluate S-1 pharmacokinetics, and to determine the efficacy and safety of this regimen as a first-line treatment for advanced gastric cancer (AGC).

Methods

Oxaliplatin was fixed at a dose of 130 mg/m2 on day 1 (D1). S-1 was administered from D1 to D14 of a 3-week cycle, and escalated by 10 mg/m2 per day from 70 mg/m2 per day up to 100 mg/m2 per day. Pharmacokinetic analyses were performed following a single dose of S-1 on D-5 and D1 of the first cycle.

Results

In phase I (n = 18), MTD was not defined. In phase II (n = 47) with the planned maximum dose, partial response was achieved in 26 patients (55.3%) and stable disease in 14 patients (29.8%). The median time to progression was 6.6 months (95% CI 4.0–9.2 months) and the median overall survival was 12.5 months (95% CI 9.2–15.9 months). Frequent grade 3/4 toxicities included thrombocytopenia (39%), neutropenia (28%), anemia (17%), and leukopenia (13%). There was one grade 5 febrile neutropenia during the first cycle.

Conclusions

The pharmacokinetics of S-1 was not influenced by oxaliplatin. S-1/Oxaliplatin combination therapy is highly active against AGC and has a favorable toxicity profile.

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Acknowledgments

We thank to Jeil Pharmaceutical Company for donation of S-1 and Sanofi Aventis for donation of oxaliplatin. We are indebted to Taiho Pharmaceutical Company for pharmacokinetic study.

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Authors and Affiliations

  1. Division of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 86 Asanbyeongwon-gil, Poongnap-dong, Songpa-gu, Seoul, 138-736, Korea

    Inkeun Park, Jae-Lyun Lee, Min-Hee Ryu, Heung Moon Chang, Tae-Won Kim, Sun-Jin Sym, Sung Sook Lee, Geundoo Jang, Changhoon Yoo & Yoon-Koo Kang

  2. Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

    Kyun-Seop Bae

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  1. Inkeun Park
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Park, I., Lee, JL., Ryu, MH. et al. Phase I/II and pharmacokinetic study of S-1 and oxaliplatin in previously untreated advanced gastric cancer. Cancer Chemother Pharmacol 65, 473–480 (2010). https://doi.org/10.1007/s00280-009-1052-3

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  • DOI: https://doi.org/10.1007/s00280-009-1052-3

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