TY - JOUR
T1 - Phase II study of preoperative gefitinib in clinical stage I non-small-cell lung cancer
AU - Lara-Guerra, Humberto
AU - Waddell, Thomas K.
AU - Salvarrey, Maria A.
AU - Joshua, Anthony M.
AU - Chung, Catherine T.
AU - Paul, Narinder
AU - Boerner, Scott
AU - Sakurada, Akira
AU - Ludkovski, Olga
AU - Ma, Clement
AU - Squire, Jeremy
AU - Liu, Geoffrey
AU - Shepherd, Frances A.
AU - Tsao, Ming Sound
AU - Leighl, Natasha B.
PY - 2009/12/20
Y1 - 2009/12/20
N2 - Purpose: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have proven efficacy in advanced non-small-cell lung cancer (NSCLC). Their role in early-stage NSCLC has not been established. Our purpose was to explore the use of preoperative gefitinib in clinical stage I NSCLC to assess tumor response, toxicity, and clinical and molecular predictors of response. Patients and Methods: Patients received gefitinib 250 mg/d for up to 28 days, followed by mediastinoscopy and surgical resection in an open-label, single-arm study. Tumor response was evaluated by Response Evaluation Criteria in Solid Tumors. Blood samples and tumor biopsies were collected and analyzed for transforming growth factor α level, EGFR protein expression, EGFR gene copy number, and EGFR (exon 19 to 21) and KRAS mutations. Results: Thirty-six patients completed preoperative treatment (median duration, 28 days; range, 27 to 30 days). Median follow-up time is 2.1 years (range, 0.86 to 3.46 years). Three patients experienced grade 3 toxicities (rash, diarrhea, and elevated ALT). Tumors demonstrated EGFR-positive protein expression in 83%, high gene copy number in 59%, EGFR mutations in 17%, and KRAS mutations in 17%. Tumor shrinkage was more frequent among women and nonsmokers. Partial response was seen in four patients (11%), and disease progression was seen in three patients (9%). The strongest predictor of response was EGFR mutation. Conclusion: Preoperative window therapy with gefitinib is a safe and feasible regimen in early NSCLC and provides a trial design that may better inform predictors of treatment response or sensitivity.
AB - Purpose: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have proven efficacy in advanced non-small-cell lung cancer (NSCLC). Their role in early-stage NSCLC has not been established. Our purpose was to explore the use of preoperative gefitinib in clinical stage I NSCLC to assess tumor response, toxicity, and clinical and molecular predictors of response. Patients and Methods: Patients received gefitinib 250 mg/d for up to 28 days, followed by mediastinoscopy and surgical resection in an open-label, single-arm study. Tumor response was evaluated by Response Evaluation Criteria in Solid Tumors. Blood samples and tumor biopsies were collected and analyzed for transforming growth factor α level, EGFR protein expression, EGFR gene copy number, and EGFR (exon 19 to 21) and KRAS mutations. Results: Thirty-six patients completed preoperative treatment (median duration, 28 days; range, 27 to 30 days). Median follow-up time is 2.1 years (range, 0.86 to 3.46 years). Three patients experienced grade 3 toxicities (rash, diarrhea, and elevated ALT). Tumors demonstrated EGFR-positive protein expression in 83%, high gene copy number in 59%, EGFR mutations in 17%, and KRAS mutations in 17%. Tumor shrinkage was more frequent among women and nonsmokers. Partial response was seen in four patients (11%), and disease progression was seen in three patients (9%). The strongest predictor of response was EGFR mutation. Conclusion: Preoperative window therapy with gefitinib is a safe and feasible regimen in early NSCLC and provides a trial design that may better inform predictors of treatment response or sensitivity.
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U2 - 10.1200/JCO.2009.22.3370
DO - 10.1200/JCO.2009.22.3370
M3 - Article
C2 - 19884551
AN - SCOPUS:74949129970
VL - 27
SP - 6229
EP - 6236
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 36
ER -