Sequential irinotecan hydrochloride/S-1 for S-1-resistant inoperable gastric cancer: A feasibility study

Takahata,Takenori; Itoh,Jugoh; Satoh,Taroh; Ishiguro,Atsushi; Matsumoto,Yoshifumi; Tanaka,Satoshi; Saitoh,Soh; Tohno,Hiroshi; Fukuda,Shinsaku; Saijo,Yasuo; Sakata,Yuh

doi:10.3892/ol.2011.435

January 2012 Volume 3 Issue 1

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January 2012 Volume 3 Issue 1

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Article

Sequential irinotecan hydrochloride/S-1 for S-1-resistant inoperable gastric cancer: A feasibility study

Authors:
- Takenori Takahata
- Jugoh Itoh
- Taroh Satoh
- Atsushi Ishiguro
- Yoshifumi Matsumoto
- Satoshi Tanaka
- Soh Saitoh
- Hiroshi Tohno
- Shinsaku Fukuda
- Yasuo Saijo
- Yuh Sakata
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Affiliations: Department of Medical Oncology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan, Department of Medical Oncology, Kinki University School of Medicine, Osakasayama 589-8511, Japan, Department of Gastroenterology and Medical Oncology, Aomori Prefectural Hospital, Aomori 030-8553, Japan, Department of Internal Medicine, Hirosaki City Hospital, Hirosaki 036-8004, Japan, Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan, Department of Medical Oncology, Misawa City Hospital, Misawa 033-0022, Japan
Pages: 89-93
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Published online on: October 4, 2011

https://doi.org/10.3892/ol.2011.435
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Abstract

Irinotecan hydrochloride (CPT-11) is reported to be involved in the downregulation of thymidylate synthase (TS), a target molecule of 5-fluorouracil (5-FU) and oral fluoropyrimidine S-1. Therefore, we hypothesized that a preceding administration of CPT-11 against S-1-resistant tumors may recover sensitivity to S-1. To this end, we planned a S-1/CPT-11 sequential therapy as a feasibility study in S-1-refractory gastric cancer patients. In the first course, CPT-11 was administered intravenously at 150 mg/m2 on days 1 and 15. Subsequently, S-1 was administered orally for 4 weeks from day 29 to 57, followed by a 2-week interval (sequential S-1/CPT-11). When the tumor showed a complete response (CR) or partial response (PR), the same dose of S-1 monotherapy was continued unless progressive disease (PD) was observed. When the response was stable disease (SD), S-1 was administered at the same dose for just 2 weeks (days 1-15), no drug was administered for the following 2 weeks (4-week cycle) and CPT-11 was administered intravenously at 100 mg/m2 on days 1 and 15 (concurrent S-1/CPT-11) unless PD was observed. In the case of PD, the study was terminated. The primary endpoint was an antitumor effect and secondary endpoints were median survival time (MST), progression-free survival (PFS), time-to-treatment failure (TTF) and safety. The response rate (RR) following the first course was only 5.9% and the most positive RR was 11.8%. The MST, median TTF and PFS were 381, 69 and 71 days, respectively. Leukocytopenia was observed in more than half of the patients. Since the RR was lower than estimated in an interim analysis, the trial was terminated and the protocol was concluded to be unfeasible.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Sequential irinotecan hydrochloride/S-1 for S-1-resistant inoperable gastric cancer: A feasibility study

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