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Time-dependent discrepancies between physician-assessed and patient-reported oxaliplatin-induced peripheral neuropathy in patients with metastatic colorectal cancer who received mFOLFOX6 plus bevacizumab: a post hoc analysis (WJOG4407GSS2)

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Abstract

Purpose

Cumulative sensory neurotoxicity induced by oxaliplatin impairs patients’ quality of life and treatment continuation. This study investigated the relationship between physician-assessed and patient-reported oxaliplatin-induced peripheral neuropathy (OIPN) during treatment of metastatic colorectal cancer (mCRC) over time.

Methods

A post hoc analysis was conducted for 191 patients with mCRC who received mFOLFOX6 plus bevacizumab in the WJOG4407G trial. Physician-assessed OIPN was graded by CTCAE every 2 weeks. Patient-reported OIPN was assessed with the FACT/GOG-Ntx (11 items, best score 44) at baseline and at 3, 6, and 9 months. Physician underestimation was defined as when the highest scores of the NTX1–4 sensory subscale/CTCAE grade were 2/0, 3/0–1, or 4/0–1, and overestimation as 0/2–3, 1/2–3, or 2/3.

Results

The median total dose (range) of oxaliplatin was 762 (85–5950) mg/m2. Overall, the least squares mean of FACT/GOG-Ntx scores (standard error), estimated by a linear mixed model, were 36 (0.8), 34 (0.9), 29 (1.0), and 27 (1.1) for CTCAE grades 0, 1, 2, and 3, respectively. FACT/GOG-Ntx scores were weakly-to-moderately correlated with CTCAE grade (Spearman’s r = − 0.24 [p = 0.0026], − 0.46 [p < 0.0001], and − 0.56 [p < 0.0001] at 3, 6, and 9 months, respectively). OIPN was underestimated in 85/159 (54%), 43/109 (39%), and 18/69 (26%) patients at 3, 6, and 9 months, respectively. In contrast, OIPN was overestimated in less than 5% of the patients at any time.

Conclusion

During early treatment, physician underestimation of OIPN in patients with mCRC is likely.

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Acknowledgments

This study was funded by Asahi Kasei Pharma. We thank the West Japan Oncology Group (WJOG) Data Center (K Mori, S Nakamura, and K Takeda).

Funding

This study was funded by a grant from Asahi Kasei Pharma.

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Authors and Affiliations

  1. Department of Medical Oncology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan

    Yuji Miura

  2. Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan

    Masahiko Ando

  3. Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan

    Kentaro Yamazaki

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

    Shuichi Hironaka

  5. Division of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan

    Narikazu Boku

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

    Kei Muro

  7. Division of Gastroenterology, University of Tsukuba, Tsukuba, Japan

    Ichinosuke Hyodo

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Contributions

Conceptualization: Yuji Miura, Masahiko Ando, and Kentaro Yamazaki; methodology: Yuji Miura and Masahiko Ando; formal analysis and investigation: Yuji Miura and Masahiko Ando; writing (original draft preparation): Yuji Miura; writing (review and editing): Ichinosuke Hyodo, Narikazu Boku, Masahiko Ando, Kentaro Yamazaki, Shuichi Hironaka, and Kei Muro; funding acquisition: Ichinosuke Hyodo and Kei Muro; supervision: Ichinosuke Hyodo and Kei Muro.

Corresponding author

Correspondence to Yuji Miura.

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Conflict of interest

Y. Miura reports receiving personal fees from ONO Pharmaceutical, Bristol Myers Squibb, MSD, and Chugai separate to the submitted work. M. Ando reports receiving personal fees from Asahi Kasei Pharma Corp. and grants from Kyowa Kirin Co. Ltd. separate to the submitted work. K. Yamazaki reports receiving personal fees from Chugai Pharma, Daiichi Sankyo, Yakult Honsha, Takeda, Bayer, Merck Serono, Taiho Pharmaceutical, Lilly, Sanofi, Ono Pharmaceutical, MSD, and Bristol-Myers Squibb separate to the submitted work. S. Hironaka reports receiving grants and personal fees from Chugai Pharma and Yakult Honsha during the conduct of the study; grants and personal fees from Sanofi, Ono Pharma, Taiho Pharma and AstraZeneca; and personal fees from Bristol-Myers Squibb Japan, Daiichi Sankyo, Lilly, Merck, Tsumura & Co., Nihonkayaku, and MSD. K.K., Shionogi, Astellas Pharma, Takeda, Boehinger Ingelheim, Kyowa Hakko Kirin, Pfizer, and Toyama Chemical Co. separate to the submitted work. N. Boku reports receiving research grants from Ono, Taiho, and Takeda and honorarium from Ono, Bristol-Myers Squibb, and Taiho separate to the submitted work. K. Muro reports receiving grants and personal fees from Ono and Sanofi; grants from Daiichi Sankyo, Parexel International, Shionogi Pharma, Sumitomo Dainippon, MSD, Pfizer, Mediscience Planning, and Solasia Pharma; and personal fees from Eli Lilly, Chugai, Takeda, Taiho, Bristol-Myers Squibb, and Bayer separate to the submitted work. I. Hyodo reports receiving grants and personal fees from Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Bristol-Myers Squibb Co., Taiho Pharmaceutical Co. Ltd., and Ono Pharmaceutical Co. Ltd.; personal fees from Eli Lilly Japan and Asahi Kasei Pharma Corp.; and grants from Takeda Pharmaceutical Co. Ltd. separate to the submitted work.

Ethical approval

The WJOG4407G trial protocol was approved by the ethics committees of all participating centers.

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Written informed consent was obtained from all enrolled patients in the WJOG4407G trial.

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Miura, Y., Ando, M., Yamazaki, K. et al. Time-dependent discrepancies between physician-assessed and patient-reported oxaliplatin-induced peripheral neuropathy in patients with metastatic colorectal cancer who received mFOLFOX6 plus bevacizumab: a post hoc analysis (WJOG4407GSS2). Support Care Cancer 29, 3715–3723 (2021). https://doi.org/10.1007/s00520-020-05891-2

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