Clinical benefit of readministration of gefitinib for initial gefitinib-responders with non-small cell lung cancer

Abstract

Background: Gefitinib, an oral agent of epidermal growth factor receptor tyrosine kinase inhibitor, has a certain efficacy against non-small cell lung cancer (NSCLC). Several predictive factors of gefitinib sensitivity have been well described. However, few studies have investigated the clinical features of gefitinib-responders. In the present study, we analyzed the response and disease progression of primary and metastatic lesions to gefitinib in responders and the results of gefitinib readministration following temporary cessation of gefitinib upon progression of initial gefitinib treatment and other treatments.

Prospective Study of Gefitinib Readministration After Chemotherapy in Patients With Advanced Non–Small-Cell Lung Cancer Who Previously Responded to Gefitinib

“…[17][18][19] Recently, Asahina et al 14 . reported results of the first prospective phase II study with a design similar to that of the present study.…”

“…Several retrospective studies regarding gefitinib readministration have shown that a prolonged gefitinib-free interval was a predictive factor for a favorable clinical result. 18,19 In addition, in cases with switching to another EGFR -TKI (erlotinib) after gefitinib failure, the EGFR-TKI-free interval with insertion of cytotoxic chemotherapy between gefitinib and erlotinib was associated with longer PFS after the initiation of erlotinib 22. It is demonstrated that tumor tissues in NSCLC could include histologically heterogeneous components and that a detection of positive or resistant EGFR mutated tumor cells could be varied with different tumor sites in certain cases 23, 2 4 . Thus, cytotoxic chemotherapy administered after a resistance to the initial EGFR-TKI may modify the heterogeneous tissue distribution in sensitive or resistant cells.…”

Predictors of Survival in Patients With Bone Metastasis of Lung Cancer

“…Gefitinib, an EGFR inhibitor, is a new molecule-targeting treatment for lung cancer. It is reported to have a considerable effect on females and nonsmokers, especially those with adenocarcinoma [6,11,12,21]. Analyses of single and multiple variables indicated better prognoses for patients with adenocarcinoma and patients treated with gefitinib.…”

“…Several recent reports suggest an epithelial growth factor receptor (EGFR) inhibitor has been effective in treating lung cancer [6,11,12,21]. The EGFR inhibitor is a new molecule-targeted agent for lung cancer that is reported to have a considerable effect on females and nonsmokers, especially those with adenocarcinoma [6,12].…”

A Phase Ib/II Study of Afatinib in Combination with Nimotuzumab in Non–Small Cell Lung Cancer Patients with Acquired Resistance to Gefitinib or Erlotinib

“…In the current study, patients with longer interval duration between prior EGFR TKI and afatinib plus nimotuzumab showed better ORR, although no statistically significant finding (36% vs. 10%, P ¼ 0.069). Several retrospective studies regarding gefitinib readministration have shown that a prolonged gefitinib-free interval was a predictive factor for a favorable clinical result (41,42), suggesting that cytotoxic chemotherapy modify the heterogeneous tissue distribution in sensitive or resistant cells.…”