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Erlotinib after gefitinib failure in relapsed non-small cell lung cancer: clinical benefit with optimal patient selection
Authors:Hata Akito  Katakami Nobuyuki  Yoshioka Hiroshige  Fujita Shiro  Kunimasa Kei  Nanjo Shigeki  Otsuka Kyoko  Kaji Reiko  Tomii Keisuke  Iwasaku Masahiro  Nishiyama Akihiro  Hayashi Hidetoshi  Morita Satoshi  Ishida Tadashi
Institution:a Division of Integrated Oncology, Institute of Biomedical Research and Innovation, 2-2, Minatojima-minamimachi, Chuo-ku, Kobe, Japan
b Department of Respiratory Medicine, Kobe City Medical Center, General Hospital, Chuo-ku, Kobe, Japan
c Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan
d Department of Biostatistics and Epidemiology, Yokohama City University Medical Center, Yokohama, Japan
Abstract:

Background

Recent reports have suggested that erlotinib therapy after gefitinib failure requires optimal patient selection to obtain clinical benefits in relapsed non-small cell lung cancer (NSCLC). However, insufficient evidence exists to determine which clinical factors best identify patients who benefit from erlotinib therapy.

Methods

One hundred twenty-five patients with relapsed NSCLC who had received erlotinib therapy after gefitinib failure were retrospectively evaluated between January 2008 and May 2009.

Results

The response rate (RR), disease control rate (DCR), and median progression-free survival (PFS) for all patients were 9% (95% confidence interval CI], 5-15%), 44% (95% CI, 35-53%), and 2.0 months (95% CI, 1.4-2.5 months), respectively. The median survival time was estimated to be 11.8 months (95% CI, 6.4-16.0 months). Using multivariate analysis, good performance status (PS), EGFR mutation-positive status, and benefit from prior gefitinib therapy were identified as significant predictive factors for disease control. Using a proportional hazards model, benefit from prior gefitinib therapy, good PS, and insertion of cytotoxic chemotherapies between gefitinib and erlotinib therapies emerged as significant predictive factors for longer PFS. Thirty-two patients with concomitant PS 0/1, benefit from prior gefitinib therapy, and insertion of cytotoxic chemotherapies between gefitinib and erlotinib therapies benefitted more from erlotinib therapy: RR, 25% (95% CI, 12-43%); DCR, 72% (95% CI, 53-86%); and median PFS, 3.4 months (95% CI, 2.4-4.9 months).

Conclusions

Higher efficacy of erlotinib after gefitinib failure can be achieved with proper patient selection criteria, including good PS, benefit from prior gefitinib therapy, and insertion of cytotoxic chemotherapies between gefitinib and erlotinib therapies.
Keywords:Erlotinib  Gefitinib  Failure  Non-small cell lung cancer  Response  Performance status
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