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A phase I trial of S-1 with oxaliplatin in patients with relapsed and metastatic colorectal cancer

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

S-1 showed clinical activity in colorectal cancer, and the preclinical data of S-1 with oxaliplatin showed synergistic activity in an animal model. This phase I study was conducted to determine the maximum tolerated dose of S-1 with oxaliplatin and to define its recommended dose for the subsequent phase II study.

Materials and Methods

Patients with untreated colorectal adenocarcinoma were eligible in this study if they had measurable lesions. S-1 was administered on days 1–14, with doses starting from 60 mg/m2 per day and escalating by 10 mg/m2 at each dose level. Oxaliplatin was given at the fixed dose of 130 mg/m2, through 2-h i.v. infusion on day 1. The treatment was repeated every 3 weeks.

Results

A total of 27 patients received six different S-1 dose levels. The dose-limiting toxicities (DLTs) were neutropenia, diarrhea, and vomiting. At dose level 5 (100 mg/m2), two patients experienced DLTs, while none of the third cohorts did. At dose level 6 (110 mg/m2), two patients experienced DLTs, and one of them died from treatment-related toxicity. The accrual was then stopped.

Conclusions

The recommended dose is S-1 100 mg/m2 on days 1–14, with 130 mg/m2 oxaliplatin on day 1, every 3 weeks. This regimen is proposed for the phase II study.

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Abbreviations

MTD:

Maximum tolerated dose

RD:

Recommended dose

DLT:

Dose-limiting toxicity

5-FU:

5-Fluorouracil

CRC:

Colorectal carcinoma

ANC:

Absolute neutrophil count

DI:

Dose intensity

TS:

Thymidylate synthase

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Acknowledgement

The S-1 that was used in this study was donated by Jeil Pharmaceutical Co., Ltd., Seoul, Korea (product of Taiho Pharmaceutical Co., Tokyo, Japan), and the oxaliplatin was provided by Sanofi-Aventis.

Conflict of interest statement

None.

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Authors and Affiliations

  1. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, #50 Ilwon-Dong, Gangnam-Gu, Seoul, 135-710, South Korea

    Hyeong Su Kim, Min Jae Park, Ji Eun Uhm, Yuna Lee, Hui Young Lee, Eun Mi Kang, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Ho Yeong Lim, Won Ki Kang & Young Suk Park

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  1. Hyeong Su Kim
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  2. Min Jae Park
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  3. Ji Eun Uhm
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  4. Yuna Lee
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  5. Hui Young Lee
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  7. Jeeyun Lee
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  9. Joon Oh Park
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  12. Young Suk Park
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Correspondence to Young Suk Park.

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Kim, H.S., Park, M.J., Uhm, J.E. et al. A phase I trial of S-1 with oxaliplatin in patients with relapsed and metastatic colorectal cancer. Int J Colorectal Dis 24, 1311–1316 (2009). https://doi.org/10.1007/s00384-009-0758-3

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  • DOI: https://doi.org/10.1007/s00384-009-0758-3

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