Comparison of adverse events and efficacy between gefitinib and erlotinib in patients with non-small-cell lung cancer: a retrospective analysis

Abstract

Previous studies have demonstrated that both gefitinib and erlotinib are markedly effective for the treatment of non-small-cell lung cancer (NSCLC) with somatic activating mutations of the epidermal growth factor receptor gene (EGFR-mt). These agents are considered to act on EGFR through the same mechanism. However, the efficacy of these agents against EGFR wild-type (-wt) NSCLC remains unclear, and the frequency of adverse events (AEs) appears to differ between them at each approved dose. Here, we conducted a retrospective analysis of AEs and drug efficacy in patients with NSCLC whose EGFR mutation status had been confirmed and who all received 250 mg gefitinib or 150 mg erlotinib once daily. The erlotinib group (n = 35) had more AEs, including rash, fatigue, stomatitis, anorexia and constipation. On the other hand, liver dysfunction and nail change were more frequent in the gefitinib group (n = 107). AEs of ≥grade 2, including rash, fatigue and nausea, were more frequent in the erlotinib group. The erlotinib group also showed more of a tendency to require dose reduction due to AEs. With regard to treatment efficacy for patients with EGFR-wt, there was no significant difference in progression-free survival between the two drug groups. However, this study has several limitations as of the nature of retrospective design; our data suggest that gefitinib and erlotinib might have almost equal efficacy for patients with EGFR-wt NSCLC, as is the case for patients with EGFR-mt tumors, although erlotinib appears to have higher toxicity than gefitinib at each approved dose.

Epidermal growth factor receptor tyrosine kinase inhibitors in elderly patients with non-small cell lung cancer

“…On the other hand, liver dysfunction and nail changes were more frequent with gefitinib. Cytochrome P450 genotype polymorphisms, especially CYP2D6, were closely related to the frequency of toxicities such as liver dysfunction with gefitinib [21]. Most toxicities associated with first-generation EGFR-TKIs are treated with supportive care.…”

Ritonavir and Efavirenz Significantly Alter the Metabolism of Erlotinib—an Observation in Primary Cultures of Human Hepatocytes That Is Relevant to HIV Patients with Cancer

“…Erlotinib is orally bioavailable and primarily metabolized by CYP3A (Ling et al, 2006;Li et al, 2007) and to a lesser extent by CYP1A1/CYP1A2 (Hughes et al, 2009). The side-effects profile of erlotinib includes burdensome skin (Ricciardi et al, 2009) and gastrointestinal tract, ocular, and rare but serious lung toxicities (Kobayashi et al, 2012;Borkar et al, 2013;Yoshida et al, 2013). Although tyrosine kinase inhibitors, such as erlotinib, do not commonly have the same lifethreatening side effects as the cytotoxic anticancer drugs, they do suffer from wide interpatient variability in pharmacokinetics [% coefficient of variation for area under the curve (AUC) and trough level is 64 and 51%, respectively] (Gao et al, 2012).…”

Safety of cranial radiotherapy concurrent with tyrosine kinase inhibitors in non-small cell lung cancer patients: A systematic review

“…When compared to the 3-13% grade P3 rash encountered with monotherapy EGFR-TKI, this percentage is slightly higher in the concurrent treated patients in this review (9-20%) [31][32][33][34][35]43]. Grade P3 rash was more often encountered with erlotinib than with gefitinib as is also known from literature, possibly because erlotinib is given at the maximum tolerated dose (MTD) and gefitinib is given at approximately one third of the MTD [54]. Although location of rash was not described, it is possible that this occurred on the scalp due to the concurrent WBRT.…”