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Risk factors of mFOLFOX6-induced hyperammonemia in patients with colorectal cancer: an observational study

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Abstract

Background

FOLFOX therapy, a standard treatment for colorectal cancer (CRC), causes a rare, but serious adverse event, hyperammonemia. However, the risk factors of hyperammonemia remain unknown.

Methods

We examined 74 patients who received mFOLFOX6 therapy with or without biologics for CRC between April 2013 and March 2018 in Yaizu City Hospital. Clinicopathological factors were retrospectively reviewed in association with hyperammonemia, and risk factors of hyperammonemia during mFOLFOX6 therapy were analyzed in 32 patients with the available data.

Results

Seven patients developed hyperammonemia, with onset exclusively on day 2 or 3 in the first cycle of therapy. They were treated with branched chain amino acid administration and hydration; however, one patient with stage G4 chronic kidney disease (CKD) died. By multivariate analysis, estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 was independently associated with hyperammonemia during FOLFOX therapy (odds ratio: 9.0, p = 0.040).

Conclusions

Reduced eGFR is considered a risk factor of developing hyperammonemia during FOLFOX therapy. Serum ammonia levels should be monitored especially during the first cycle of FOLFOX therapy in patients with CKD stage G3 or higher.

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Data availability

The datasets and analyzed data from the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Surgical Oncology, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Kazuaki Okamoto, Hiroaki Nozawa, Yuuki Iida, Kazushige Kawai, Kazuhito Sasaki, Koji Murono & Soichiro Ishihara

  2. Department of Surgery, Yaizu City Hospital, 1000, Doubara, Yaizu-shi, Shizuoka, 425-8505, Japan

    Kazuaki Okamoto, Kumiko Hongo, Yuuki Iida, Yusuke Kita, Yukio Ishihara, Naoki Takabayashi, Ryo Kobayashi & Takeyuki Hiramatsu

  3. Department of Surgery, Hiratsuka City Hospital, 1-19-1, Minamihara, Hiratsuka-shi, Kanagawa, 254-0065, Japan

    Kumiko Hongo

Authors
  1. Kazuaki Okamoto
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  2. Hiroaki Nozawa
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  4. Yuuki Iida
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Contributions

KO, KH, YI, YK, YI, NK, RK and TH developed the study design and concept, retrieved the data of patients and carried out the analysis. KO, HN, KH, YI, KK, KS, KM, TH and SI participated in writing and revising the manuscript critically. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Kazuaki Okamoto.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This study was approved by the Ethics Committees of Yaizu City Hospital (No. 239).

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Okamoto, K., Nozawa, H., Hongo, K. et al. Risk factors of mFOLFOX6-induced hyperammonemia in patients with colorectal cancer: an observational study. Int J Clin Oncol 26, 1477–1484 (2021). https://doi.org/10.1007/s10147-021-01932-w

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  • DOI: https://doi.org/10.1007/s10147-021-01932-w

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