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Two versus three courses of preoperative cisplatin and fluorouracil plus docetaxel for treating locally advanced esophageal cancer: short-term outcomes of a multicenter randomized phase II trial

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Abstract

Objective

To compare short-term outcomes between two- vs. three courses of neoadjuvant chemotherapy (NAC) to clarify the optimal treatment for esophageal squamous cell cancer (ESCC) in a multicenter, randomized, phase II trial.

Background

An optimal number of NAC cycles remains to be established for locally advanced ESCC.

Methods

Patients with locally advanced ESCC were randomly assigned to either two (N = 91) or three (N = 89) courses of DCF (70 mg/m2 intravenous docetaxel and 70 mg/m2 intravenous cisplatin on day 1, and a continuous 700 mg/m2 fluorouracil infusion for 5 days) every 3 weeks followed by surgery. We compared the two groups for perioperative parameters, adverse events, and the response to NAC.

Results

The two- and three-course groups showed similar completion rates and overall NAC dose reductions. Although the two-course group showed significantly lower overall grades 3–4 leukopenia and anemia compared to the three-course group, the two groups had similar overall toxicity rates. Postoperative complications were not significantly different between the two groups, except arrhythmia (13 vs. 0%, P = 0.0007). Only two postoperative in-hospital deaths occurred in the three-course group, due to sepsis following severe pneumonia. Compared to the two-course group, the three-course group was associated with a significantly better clinical response (42.9 vs. 65.2%, P = 0.0027) and a relatively higher rate of pathological complete response (9.1 vs. 15.3%, P = 0.212).

Conclusion

Both two- and three-course DCF regimens in the NAC setting seemed to be equally feasible in locally advanced ESCC patients. Additional DCF courses led to a better NAC response without increasing the incidence of adverse events or postoperative morbidity.

Clinical Trial Registration

University Hospital Medical Information Network Clinical Trials Registry of Japan (Identification Number UMIN 000015788).

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Acknowledgements

The authors would like to thank the staff of all the centers that participated in data collection for this study.

Funding

The authors did not receive any funding.

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Authors and Affiliations

  1. Faculty of Medicine, Department of Surgery, Kindai University, Osaka-Sayama, Osaka, Japan

    Osamu Shiraishi, Yutaka Kimura & Takushi Yasuda

  2. Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka University, 2-2-E2, Yamada-oka, Suita, Osaka, 565-0871, Japan

    Tomoki Makino, Makoto Yamasaki, Koji Tanaka, Kotaro Yamashita, Tomo Ishida & Yuichiro Doki

  3. Department of Digestive Surgery, Osaka International Cancer Institute, Osaka, Osaka, Japan

    Keijiro Sugimura, Hiroshi Miyata & Masahiko Yano

  4. Department of Surgery, Osaka General Medical Center, Osaka, Osaka, Japan

    Masaaki Motoori & Kazumasa Fujitani

  5. Department of Surgery, Kansai Rosai Hospital, Amagasaki, Hyogo, Japan

    Atsushi Takeno

  6. Department of Surgery, National Hospital Organization, Osaka National Hospital, Chuo Ward, Osaka, Japan

    Motohiro Hirao

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

    Taroh Satoh

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  1. Osamu Shiraishi
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Corresponding author

Correspondence to Tomoki Makino.

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Ethical Statement

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki 35 Declaration of 1964 and later versions.

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The authors declare no conflicts of interest.

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Tomoki Makino: equally-contributed first author.

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Shiraishi, O., Makino, T., Yamasaki, M. et al. Two versus three courses of preoperative cisplatin and fluorouracil plus docetaxel for treating locally advanced esophageal cancer: short-term outcomes of a multicenter randomized phase II trial. Esophagus 18, 825–834 (2021). https://doi.org/10.1007/s10388-021-00831-3

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  • DOI: https://doi.org/10.1007/s10388-021-00831-3

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