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Phase I trial of 5-FU, docetaxel, and nedaplatin (UDON) combination therapy for recurrent or metastatic esophageal cancer

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Abstract

Purpose

The aims of this dose-escalating phase I study were to determine the maximum tolerable dose (MTD) and recommended dose (RD) of 5-fluorouracil (5-FU), docetaxel, and nedaplatin (UDON) combination therapy for future phase II studies, and to evaluate the safety and efficacy of this regimen in patients with untreated recurrent or metastatic esophageal cancer.

Methods

Patients were administered 5-FU on days 1–5, docetaxel on days 1 and 15, and nedaplatin on day 1 at 4-week intervals. The dose levels of 5-FU/docetaxel/nedaplatin were escalated as follows (mg/m2): level 1, 800/30/80; level 2, 800/30/90; and level 3, 800/35/90. Toxicity was evaluated using Common Terminology Criteria for Adverse Events version 4.0.

Results

Overall, nine patients were enrolled in this study. All patients had an Eastern Cooperative Oncology Group performance status of 0 or 1 and were diagnosed with squamous cell carcinoma. No dose-limiting toxicity was observed at any level, and planned dose escalation was completed without reaching the MTD. No grade 4 or higher toxicity was observed in this study. The observed grade 3 hematological toxicities included neutropenia in five patients (55.6 %) and leukopenia in three patients (33.3 %). None of the patients developed febrile neutropenia, and no grade 3 or 4 non-hematological toxicities were observed. The overall response rate was 77.8 %, including two complete responses, and the disease control rate was 100 %.

Conclusion

The RD of UDON was identified as level 3. The good tolerability and high antitumor efficacy of this regimen warrant further evaluation in this setting.

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Acknowledgments

We thank Asami Kitano and Tomoka Yamada from the Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka, Japan.

Conflict of interest

The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Department of Medical Oncology, Faculty of Medicine, Kinki University, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan

    Shinya Ueda, Hisato Kawakami, Shinichi Nishina, Tsutomu Sakiyama, Yoshikane Nonagase, Takafumi Okabe, Takao Tamura & Kazuhiko Nakagawa

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  1. Shinya Ueda
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  2. Hisato Kawakami
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  3. Shinichi Nishina
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  4. Tsutomu Sakiyama
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Correspondence to Hisato Kawakami.

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Ueda, S., Kawakami, H., Nishina, S. et al. Phase I trial of 5-FU, docetaxel, and nedaplatin (UDON) combination therapy for recurrent or metastatic esophageal cancer. Cancer Chemother Pharmacol 76, 279–285 (2015). https://doi.org/10.1007/s00280-015-2799-3

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  • DOI: https://doi.org/10.1007/s00280-015-2799-3

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