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A Phase II Study of Modified FOLFOX6 for Advanced Gastric Cancer Refractory to Standard Therapies

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Abstract

Introduction

In patients with advanced gastric cancer refractory to chemotherapy, the treatment options are limited. Via this phase II study, we aimed to assess the efficacy and safety of oxaliplatin in combination with 5-fluorouracil and l-leucovorin (modified FOLFOX6).

Methods

Patients who had histologically confirmed metastatic gastric cancer refractory to ≥ two previous chemotherapy regimens were included. The primary endpoint was the overall response rate (ORR) by an independent central review. According to an assumption of a threshold ORR of 10% and expected ORR of 25%, with α = 0.05 and β = 0.20, at least 33 patients were required. The secondary endpoints included overall survival (OS), progression-free survival (PFS), quality of life measured by EQ-5D, and safety.

Results

Among the 35 enrolled patients, 33 were included in the primary analysis. All patients previously received fluoropyrimidines, cisplatin, and taxanes, and 24 (73%) were pretreated with irinotecan. The confirmed ORR was 27% [95% confidence interval (CI) 13–46]. The median PFS and OS were 2.2 (95% CI 1.2–3.2) and 5.6 (95% CI 4.1–7.0) months, respectively. In the multivariate analyses, immunotherapy within 90 days and a Glasgow Prognostic Score of 0 were associated with better treatment outcomes. The most common grade ≥ 3 adverse event was neutropenia (36%), and no febrile neutropenia was observed. The median EQ-5D scores did not change from baseline at 2, 4, and 8 weeks (p value = 0.38, 0.79, and 0.98, respectively).

Conclusion

Modified FOLFOX6 (mFOLFOX6) showed substantial activity and acceptable toxicity for chemotherapy-refractory advanced gastric cancer.

Trial Registration

UMIN Clinical Trial Registry (UMIN000016416).

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Acknowledgements

The authors thank Dr. M. Nomura from Kyoto University Graduate School of Medicine for tumor assessment. We also sincerely appreciate all the patients who received treatment and were enrolled in this study.

Funding

No funding or sponsorship was received for this study. The journal’s Rapid Service Fee was funded by the authors.

Editorial Assistance

The authors would like to thank Enago (www.enago.jp) for the English language review.

Authorship

All the authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Disclosures

Seiichiro Mitani reports payment for lectures from Taiho Pharmaceutical Co., Eli Lilly, Takeda Pharmaceutical Co., and Ono Pharmaceutical Co. Shigenori Kadowaki reports grants and payment for lectures from Eli Lilly and Taiho Pharmaceutical Co., grants from Ono Pharmaceutical Co. and Bristol-Myers Squibb, and payment for lectures from Yakult Honsha Co., Ltd., Chugai Pharmaceutical Co., Ltd., Bayer, and Merck. Chihiro Kondoh reports payment for lectures from Sanofi, Janssen Pharmaceutical K.K., NIPPON SHINYAKU, Eisai, MSD, Bristol-Myers Squibb, Chugai Pharmaceutical Co., and Takeda Pharmaceutical Co. Toshiki Masuishi reports grants from Daiichi Sankyo, MSD and Ono Pharmaceutical Co., and payment for lectures from Taiho Pharmaceutical Co., Chugai Pharmaceutical Co., Ltd., Eli Lilly, Takeda Pharmaceutical Co., Merck and Bayer. Yukiya Narita reports payment for lectures from Bristol-Myers Squibb, Ono Pharmaceutical Co., Nihon Kayaku and Taiho Pharmaceutical Co. Hiroya Taniguchi reports grants and payment for lectures from Takeda Pharmaceutical Co., grants from Daiichi Sankyo and Sysmex, and payment for lectures from Taiho Pharmaceutical Co., Chugai Pharmaceutical Co., Ltd., and Eli Lilly. Kei Muro reports grants and payment for lectures from Sanofi, grants from MSD, Daiichi Sankyo, Sumitomo Dainippon Pharma, Shionogi, Parexel International, Mediscience Planning and Pfizer, and payment for lectures from Taiho Pharmaceutical Co., Chugai Pharmaceutical Co., Ltd., Eli Lilly, Takeda Pharmaceutical Co., Ono Pharmaceutical Co., Bayer, and Bristol-Myers Squibb. All remaining authors (Azusa Komori, Isao Oze, Kyoko Kato, Kazunori Honda, Masashi Ando, Tsutomu Tanaka and Masahiro Tajika) have nothing to disclose.

Compliance with Ethics Guidelines

The protocol was approved by the institutional review board of Aichi Cancer Center Hospital. This study was approved by the institutional review boards and registered in the UMIN Clinical Trial Registry (UMIN000016416). Written informed consent was obtained from each patient before study enrollment, and the study was conducted in accordance with the Declaration of Helsinki.

Data Availability

The datasets generated during and/or analyzed during the current study are not publicly available, but are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan

    Seiichiro Mitani, Shigenori Kadowaki, Azusa Komori, Chihiro Kondoh, Kyoko Kato, Toshiki Masuishi, Kazunori Honda, Yukiya Narita, Hiroya Taniguchi, Masashi Ando & Kei Muro

  2. Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan

    Seiichiro Mitani

  3. Department of Medical Oncology and Hematology, Oita University Faculty of Medicine, Oita, Japan

    Azusa Komori

  4. Department of Medical Oncology, Toranomon Hospital, Tokyo, Japan

    Chihiro Kondoh

  5. Division of Cancer Epidemiology and Prevention, Aichi Cancer Center, Nagoya, Japan

    Isao Oze

  6. Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan

    Hiroya Taniguchi

  7. Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan

    Tsutomu Tanaka & Masahiro Tajika

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  1. Seiichiro Mitani
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Corresponding author

Correspondence to Shigenori Kadowaki.

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Mitani, S., Kadowaki, S., Komori, A. et al. A Phase II Study of Modified FOLFOX6 for Advanced Gastric Cancer Refractory to Standard Therapies. Adv Ther 37, 2853–2864 (2020). https://doi.org/10.1007/s12325-020-01358-2

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