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Cancer Chemother Pharmacol. 2016 Nov;78(5):941-947. Epub 2016 Sep 2.

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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Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1, Shikatacho, Kitaku, Okayama, 700-8558, Japan.
Department of Respiratory Medicine, Kurashiki Central Hospital, Okayama, Japan.
Department of Respiratory Medicine, National Hospital Organization Iwakuni Medical Center, Iwakuni, Japan.
Center for Clinical Oncology, Okayama University Hospital, Okayama, Japan.
Department of General Internal Medicine 4, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan.



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.


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.


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).


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


EGFR-tyrosine kinase inhibitor; Gefitinib; Hepatic dysfunction; Lung cancer; Overweight

[Indexed for MEDLINE]

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