BACKGROUND: Improvements in first-line therapy of advanced non-small-cell lung cancer (NSCLC) have increased the need for effective second-line treatment options. In a Phase II trial of the anticancer drug gefitinib (IRESSA), greater efficacy was observed in Japanese compared with non-Japanese patients. Furthermore, results from a placebo-controlled Phase III trial (IRESSA Survival Evaluation in Lung cancer [ISEL]) showed that treatment with gefitinib was not associated with a statistically significant improvement in survival in either the overall or adenocarcinoma co-primary populations, although there was marked heterogeneity in survival outcomes between patient groups, with patients of Asian origin achieving a significant survival benefit with gefitinib compared with placebo. OBJECTIVE: To review the benefit:risk profile of gefitinib in Asian patients with advanced NSCLC. RESEARCH DESIGN AND METHODS: We identified and reviewed 31 reports (each with >or= 25 patients) of clinical experience with gefitinib 250 mg/day in Asia involving a total of > 2000 patients with refractory NSCLC in Japan, China, Korea and Taiwan by searching EMBASE and Medline databases for publications between 1 January 2003 and 1 July 2005. RESULTS AND DISCUSSION: In the majority of these reports, objective response rates of > 25% and disease control rates of > 60% have been described. Treatment with gefitinib resulted in a median time to progression of > 3 months and a median survival time of > 6 months in most studies. These 31 reports also demonstrated the efficacy of gefitinib in patients with secondary brain metastases, those with poor performance status (PS) and in patients receiving the drug as first-line treatment. Female gender, adenocarcinoma histology, non-smoking history, good PS and the presence of multiple lung metastases are associated with improved responsiveness to gefitinib. Reflecting the results of previous clinical trials, the reports indicate that gefitinib is generally well tolerated by Asian patients. The incidence of interstitial lung disease appears to be higher in Japanese than non-Japanese patients, although the reasons for this are not clear. Recent findings regarding cellular and genetic factors that may underlie the increased responsiveness to gefitinib among Asian patients are discussed.
BACKGROUND: Improvements in first-line therapy of advanced non-small-cell lung cancer (NSCLC) have increased the need for effective second-line treatment options. In a Phase II trial of the anticancer drug gefitinib (IRESSA), greater efficacy was observed in Japanese compared with non-Japanese patients. Furthermore, results from a placebo-controlled Phase III trial (IRESSA Survival Evaluation in Lung cancer [ISEL]) showed that treatment with gefitinib was not associated with a statistically significant improvement in survival in either the overall or adenocarcinoma co-primary populations, although there was marked heterogeneity in survival outcomes between patient groups, with patients of Asian origin achieving a significant survival benefit with gefitinib compared with placebo. OBJECTIVE: To review the benefit:risk profile of gefitinib in Asian patients with advanced NSCLC. RESEARCH DESIGN AND METHODS: We identified and reviewed 31 reports (each with >or= 25 patients) of clinical experience with gefitinib 250 mg/day in Asia involving a total of > 2000 patients with refractory NSCLC in Japan, China, Korea and Taiwan by searching EMBASE and Medline databases for publications between 1 January 2003 and 1 July 2005. RESULTS AND DISCUSSION: In the majority of these reports, objective response rates of > 25% and disease control rates of > 60% have been described. Treatment with gefitinib resulted in a median time to progression of > 3 months and a median survival time of > 6 months in most studies. These 31 reports also demonstrated the efficacy of gefitinib in patients with secondary brain metastases, those with poor performance status (PS) and in patients receiving the drug as first-line treatment. Female gender, adenocarcinoma histology, non-smoking history, good PS and the presence of multiple lung metastases are associated with improved responsiveness to gefitinib. Reflecting the results of previous clinical trials, the reports indicate that gefitinib is generally well tolerated by Asian patients. The incidence of interstitial lung disease appears to be higher in Japanese than non-Japanese patients, although the reasons for this are not clear. Recent findings regarding cellular and genetic factors that may underlie the increased responsiveness to gefitinib among Asian patients are discussed.
Authors: Danan Li; Hongbin Ji; Sara Zaghlul; Kate McNamara; Mei-Chih Liang; Takeshi Shimamura; Shigeto Kubo; Masaya Takahashi; Lucian R Chirieac; Robert F Padera; Andrew M Scott; Achim A Jungbluth; Webster K Cavenee; Lloyd J Old; George D Demetri; Kwok-Kin Wong Journal: J Clin Invest Date: 2007-01-25 Impact factor: 14.808
Authors: A D Roses; M W Lutz; H Amrine-Madsen; A M Saunders; D G Crenshaw; S S Sundseth; M J Huentelman; K A Welsh-Bohmer; E M Reiman Journal: Pharmacogenomics J Date: 2009-12-22 Impact factor: 3.550
Authors: King Pan Ng; Axel M Hillmer; Charles T H Chuah; Wen Chun Juan; Tun Kiat Ko; Audrey S M Teo; Pramila N Ariyaratne; Naoto Takahashi; Kenichi Sawada; Yao Fei; Sheila Soh; Wah Heng Lee; John W J Huang; John C Allen; Xing Yi Woo; Niranjan Nagarajan; Vikrant Kumar; Anbupalam Thalamuthu; Wan Ting Poh; Ai Leen Ang; Hae Tha Mya; Gee Fung How; Li Yi Yang; Liang Piu Koh; Balram Chowbay; Chia-Tien Chang; Veera S Nadarajan; Wee Joo Chng; Hein Than; Lay Cheng Lim; Yeow Tee Goh; Shenli Zhang; Dianne Poh; Patrick Tan; Ju-Ee Seet; Mei-Kim Ang; Noan-Minh Chau; Quan-Sing Ng; Daniel S W Tan; Manabu Soda; Kazutoshi Isobe; Markus M Nöthen; Tien Y Wong; Atif Shahab; Xiaoan Ruan; Valère Cacheux-Rataboul; Wing-Kin Sung; Eng Huat Tan; Yasushi Yatabe; Hiroyuki Mano; Ross A Soo; Tan Min Chin; Wan-Teck Lim; Yijun Ruan; S Tiong Ong Journal: Nat Med Date: 2012-03-18 Impact factor: 53.440