A phase II study of combination therapy with 5′-deoxy-5-fluorouridine and cisplatin in the treatment of advanced gastric cancer with primary foci

Authors

  • Wasaburo Koizumi M.D.,

    Assistant Professor of Internal Medicine, Corresponding author
    1. Japan Gastric Cancer Study Group, Tokyo, Japan
    • Department of Gastroenterology, East Hospital, Kitasato University, School of Medicine, 2–1–1, Asamizodai, Sagamihara-Shi, Kanagawa Prefecture, Japan, 228
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    • Assistant Professor of Internal Medicine, Department of Gastroenterology, East Hospital, Kitasato University, School of Medicine, Asamizodai, Sagamihara-Shi, Kanagawa Prefecture, Japan.

  • Minoru Kurihara M.D.,

    1. Japan Gastric Cancer Study Group, Tokyo, Japan
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    • Professor of Internal Medicine, Department of Gastroenterology, Toyosu Hospital, Showa University, School of Medicine, Tokyo, Japan; and Chairman of the Japan Gastric Cancer Study Group, Tokyo, Japan.

  • Tadashi Sasai M.D.,

    1. Japan Gastric Cancer Study Group, Tokyo, Japan
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    • Chief, Internal Medicine, National Okayama Hospital. 2–13–1, Minamigata, Okayama-Shi, Okayama Prefecture, Japan, 700.

  • Shigeaki Yoshida M.D.,

    1. Japan Gastric Cancer Study Group, Tokyo, Japan
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    • Chief, Gastroenterology, National Cancer Center Hospital, Tsukiji, Chuo-Ku, Tokyo, Japan.

  • Kimitomo Morise M.D.,

    1. Japan Gastric Cancer Study Group, Tokyo, Japan
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    • Department of Internal Medicine I, Nagoya University, School of Medicine, Tsurumai-Cho, Showa-Ku, Nagoya-Shi, Aichi Prefecture, Japan.

  • Akimichi Imamura M.D.,

    1. Japan Gastric Cancer Study Group, Tokyo, Japan
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    • Chief, Gastroenterology, Sapporo Kosei Hospital, Kitashijo, Chuo-Ku, Sapporo-Shi, Hokkaido, Japan.

  • Shugo Akazawa M.D.,

    1. Japan Gastric Cancer Study Group, Tokyo, Japan
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    • Chief, Gastroenterology, Saitama Cancer Center Hospital, Komuro, Inamachi, Kitaadachi-Gun, Saitama Prefecture, Japan.

  • Takashi Betsuyaku M.D.,

    1. Japan Gastric Cancer Study Group, Tokyo, Japan
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    • Chief, Gastroenterology, National Sapporo Hospital, 4-Jo, Kikusui, Shiraishi-Ku, Sapporo-Shi, Hokkaido, Japan.

  • Shunji Ohkubo M.D.,

    1. Japan Gastric Cancer Study Group, Tokyo, Japan
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    • Chief, Internal Medicine I, Hiraga Sogo Hospital, Ekimae-Cho, Yokote-Shi, Akita Prefecture, Japan.

  • Hiroshi Takahashi M.D.,

    1. Japan Gastric Cancer Study Group, Tokyo, Japan
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    • Assistant Professor, Clinical Cancer Chemotherapy, The Research Institute for Tuberculosis and Cancer, Tohoku University, Seiryo-Cho, Aoba-Ku, Sendai-Shi, Miyagi Prefecture, Japan.

  • Toshikazu Akiya M.D.,

    1. Japan Gastric Cancer Study Group, Tokyo, Japan
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    • Chief, Internal Medicine, Toumou Hospital, Gunma Cancer Center. 617–1, Takabayashi, Ohta-Ku, Gunma Prefecture, JAPAN, 373.

  • Tsutomu Hamada M.D.,

    1. Japan Gastric Cancer Study Group, Tokyo, Japan
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    • Lecturer, Gastroenterology, School of Medicine, Juntendo University, Hongo, Bunkyo-Ku, Tokyo, Japan.

  • Atsushi Kiyohashi M.D.

    1. Japan Gastric Cancer Study Group, Tokyo, Japan
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    • Chief, Gastroenterology, Kanagawa Cancer Center Hospital, Nakano-Cho, Asahi-Ku, Yokohama-Shi, Kanagawa Prefecture, Japan.


Abstract

Background. 5′-Deoxy-5-fluorouridine (5′-DFUR, doxifluridine) is a recently developed prodrug of oral 5-fluorouracil (5-FU), which is used clinically in Japan for the treatment of gastric, colorectal, and breast cancer. 5-FU has been reported to act synergistically with cisplatin (CDDP) in experimental and clinical studies. The authors conducted a multicenter Phase II study of combination therapy with 5′-DFUR and CDDP to evaluate the therapeutic usefulness of this regimen in the treatment of unresectable and advanced gastric cancers with primary foci. None of the patients had previously undergone chemotherapy. Their ages ranged from 27 to 75 years and performance status was grade 0 to 3.

Methods. 5′-DFUR (1400 mg/m2/d) was administered orally on days 1 through 4 and 15 through 18, and CDDP (80 mg/m2/d) was injected intravenously on day 5. This treatment cycle was repeated every 4 weeks. An independent panel of specialists evaluated the clinical response.

Results. Fifty-one patients were studied. Clinical evaluation of response was possible in 43 patients who met the protocol requirements. The overall response rate was 50.0% (14 of 28, 95% confidence limits, 30.7%–69.4%) for patients with measurable lesions. The median duration of response was 5.2 months (156 days). The overall median survival time was 8.9 months (268 days) for evaluated patients. Therapeutic toxicity of World Health Organization (WHO) grade ≧ 3 was manifested as anorexia and nausea or vomiting in 20.9% and 18.6% of the patients, respectively. However myelotoxicity and nephrotoxicity of WHO grades 3 and 4 occurred in less than 10% of the patient group. No drug-related mortality occurred.

Conclusions. Combined therapy with 5′-DFUR and CDDP is a safe and effective treatment regimen for advanced gastric cancers with primary foci which stresses the patient's quality of life, especially when used in an outpatient setting.

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