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Potential influence of being overweight on the development of hepatic dysfunction in Japanese patients with EGFR-mutated non-small cell lung cancer undergoing gefitinib monotherapy: the Okayama Lung Cancer Study Group experience

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Abstract

Background

Being overweight has been reported to induce hepatic dysfunction during cytotoxic chemotherapy. Severe hepatic dysfunction can also be observed during gefitinib monotherapy, leading to interrupted or discontinued treatment. However, whether being overweight is a risk factor during gefitinib therapy is unknown.

Methods

We retrospectively reviewed 183 Japanese patients with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor-naïve non-small cell lung cancer (NSCLC) harboring EGFR mutations, who received gefitinib monotherapy between July 2007 and February 2014. We defined being overweight as having a body mass index (BMI) ≥ 25 kg/m2 and assessed its potential relationship with ≥grade 2 hepatic dysfunction.

Results

The patient demographics were as follows: 114 women; median age 72 years (range 42–95 years); BMI ≥ 25 kg/m2, n = 32; performance status 0–1, n = 136; stage IIIB/IV, n = 141; and major EGFR mutations, n = 171. Hepatic dysfunction ≥grade 2 during the gefitinib therapy was observed in 44 (24.0 %) patients, 22 (50.0 %) of whom interrupted or discontinued treatment. The median duration from gefitinib administration to the development of hepatic dysfunction was 56 days (range 6–1,352 days). Overweight patients were more likely to develop hepatic dysfunction ≥grade 2 compared to non-overweight patients according to a multivariate analysis adjusted for several confounding factors (hazard ratio 2.24; 95 % confidence interval 1.01–4.95; p = 0.046).

Conclusion

These results suggest that being overweight may induce hepatic dysfunction during gefitinib monotherapy in Japanese patients with EGFR-mutated NSCLC.

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Acknowledgments

The authors acknowledge the assistance and input of Sato E (Kurashiki Central Hospital) during this trial. The authors are also deeply grateful for all participants who made this study possible. Data interpretation and reporting are the sole responsibilities of the authors. NO and KH had full access to all of the data in the study, are responsible for the integrity of the data and accuracy of the data analysis, and contributed to the study design, data collection, analyses, and writing of the manuscript. All other co-authors contributed to writing of the manuscript. This study has been conducted with a support from the Center for Innovative Clinical Medicine, Okayama University Hospital, Japan.

Funding

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Authors and Affiliations

  1. Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan

    Naohiro Oda, Katsuyuki Hotta, Eiki Ichihara, Yuka Kato, Kiichiro Ninomiya, Daisuke Minami, Takashi Ninomiya, Kadoaki Ohashi, Akiko Sato, Mitsune Tanimoto & Katsuyuki Kiura

  2. Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1, Shikatacho, Kitaku, Okayama, 700-8558, Japan

    Katsuyuki Hotta

  3. Department of Respiratory Medicine, Kurashiki Central Hospital, Okayama, Japan

    Hiroshige Yoshioka

  4. Department of Respiratory Medicine, National Hospital Organization Iwakuni Medical Center, Iwakuni, Japan

    Kenichiro Kudo

  5. Center for Clinical Oncology, Okayama University Hospital, Okayama, Japan

    Toshio Kubo & Masahiro Tabata

  6. Department of General Internal Medicine 4, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan

    Nagio Takigawa

Authors
  1. Naohiro Oda
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  2. Katsuyuki Hotta
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  3. Hiroshige Yoshioka
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  4. Kenichiro Kudo
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  5. Eiki Ichihara
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  6. Yuka Kato
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  8. Daisuke Minami
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  9. Takashi Ninomiya
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  11. Kadoaki Ohashi
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  12. Akiko Sato
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  13. Nagio Takigawa
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  14. Masahiro Tabata
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  15. Mitsune Tanimoto
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  16. Katsuyuki Kiura
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Corresponding author

Correspondence to Katsuyuki Hotta.

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Conflict of interest

KH has received honoraria from AstraZeneca, Eli Lilly Japan, Daiichi-Sankyo Pharmaceutical, Boehringer-Ingelheim, Nihon Kayaku, Taiho Pharmaceutical, and Chugai Pharmaceutical. KH also has received research funding from Eli Lilly Japan, MSD, and Chugai Pharmaceutical. HY received honoraria from AstraZeneca, Chugai Pharmaceutical, Boehringer-Ingelheim in Japan, and Eli Lilly Japan. NT has received honoraria from AstraZeneca, Daiichi-Sankyo Pharmaceutical, Chugai Pharmaceutical, Taiho Pharmaceutical, Pfizer Inc. Japan, Boehringer-Ingelheim in Japan, Eisai, and Kyowa-Hakko Kirin. NT also received research donated funds from Nihon Kayaku, AstraZeneca, Chugai Pharmaceutical, Taiho Pharmaceutical, Pfizer Inc. Japan, Boehringer-Ingelheim in Japan, and Kyowa-Hakko Kirin. KK has received honoraria from Eli Lilly Japan, Nihon Kayaku, AstraZeneca, Daiichi-Sankyo Pharmaceutical, Chugai Pharmaceutical, Taiho Pharmaceutical, and Sanofi-Aventis. All other authors declare that they have no conflicts of interest relating to this study.

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Oda, N., Hotta, K., Yoshioka, H. et al. Potential influence of being overweight on the development of hepatic dysfunction in Japanese patients with EGFR-mutated non-small cell lung cancer undergoing gefitinib monotherapy: the Okayama Lung Cancer Study Group experience. Cancer Chemother Pharmacol 78, 941–947 (2016). https://doi.org/10.1007/s00280-016-3146-z

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  • DOI: https://doi.org/10.1007/s00280-016-3146-z

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