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A phase I trial of combination therapy using gemcitabine and S-1 concurrent with full-dose radiation for resectable pancreatic cancer

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Abstract

Purpose

Use of the fourth-generation oral fluoropyrimidine S-1 together with gemcitabine has shown striking anticancer effects. In this single-arm phase I trial of preoperative combination therapy using gemcitabine and S-1 concurrently with radiotherapy, we verified the safety and feasibility and determined the maximum-tolerated dose of each drug in patients with resectable pancreatic cancer.

Methods

A standard 3+3 dose escalation scheme was used. Patients with cytologically or histologically proven resectable pancreatic ductal adenocarcinoma were administered 30-min intravenous gemcitabine infusions on days 1, 8, 22, and 29 and S-1 orally on days 1–5, 8–12, 22–26, and 29–33. A total radiation dose of 50.4 Gy (1.8 Gy/day, 5 times per week, 28 fractions) was concurrently delivered. Surgical exploration was scheduled 4–7 weeks after the final radiation fraction.

Results

Twenty-one patients were enrolled. No treatment-related deaths occurred during this study. Recommended doses were determined to be 80 mg/m2 of S-1 daily and 1,000 mg/m2 of gemcitabine. CA19-9 was reduced to <50 % of baseline values in 12 (75 %) of 16 measurable patients. Nineteen of 21 enrolled patients successfully underwent surgical resection.

Conclusions

Preoperative chemoradiotherapy consisting of gemcitabine and S-1 concurrent with full-dose radiation is feasible and well tolerated.

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Abbreviations

PDAC:

Pancreatic ductal adenocarcinoma

CTCAE:

Common Terminology Criteria for Adverse Events

MTD:

Maximum-tolerated dose

RD:

Recommended dose

DLT:

Dose-limiting toxicity

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Conflict of interest

None.

Funding

This study was supported in part by Japanese Foundation for Multidisciplinary Treatment of Cancer.

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Authors and Affiliations

  1. Department of Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka E-2, Suita 565-0871, Osaka, Japan

    Hidetoshi Eguchi, Hiroaki Nagano, Shogo Kobayashi, Koichi Kawamoto, Hiroshi Wada, Naoki Hama, Yoshito Tomimaru, Hirofumi Akita, Masaki Mori & Yuichiro Doki

  2. Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Osaka, Japan

    Daisuke Sakai, Taroh Satoh & Toshihiro Kudo

  3. Department of Radiation Oncology, Graduate School of Medicine, Osaka University, Osaka, Japan

    Fumiaki Isohashi

  4. Clinical Study Group of Osaka University (CSGO), Hepato-Biliary-Pancreatic Group, Osaka, Japan

    Hidetoshi Eguchi, Hiroaki Nagano, Shogo Kobayashi, Koichi Kawamoto, Hiroshi Wada, Naoki Hama, Yoshito Tomimaru, Hirofumi Akita, Daisuke Sakai, Taroh Satoh, Toshihiro Kudo, Fumiaki Isohashi, Masaki Mori & Yuichiro Doki

Authors
  1. Hidetoshi Eguchi
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  2. Hiroaki Nagano
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  3. Shogo Kobayashi
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  4. Koichi Kawamoto
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  5. Hiroshi Wada
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  7. Yoshito Tomimaru
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  8. Hirofumi Akita
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  11. Toshihiro Kudo
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  12. Fumiaki Isohashi
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  13. Masaki Mori
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  14. Yuichiro Doki
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Corresponding author

Correspondence to Hidetoshi Eguchi.

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UMIN Clinical Trials Registry Number: 000002649.

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Eguchi, H., Nagano, H., Kobayashi, S. et al. A phase I trial of combination therapy using gemcitabine and S-1 concurrent with full-dose radiation for resectable pancreatic cancer. Cancer Chemother Pharmacol 73, 309–315 (2014). https://doi.org/10.1007/s00280-013-2357-9

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  • DOI: https://doi.org/10.1007/s00280-013-2357-9

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