INTRODUCTION: A feasibility study was performed to examine the safety and toxicity profile of daily gefitinib (250 mg) administration with concurrent definitive thoracic radiation therapy (TRT) in patients with unresectable non-small cell lung cancer (NSCLC) of stage III. METHODS: Patients received a 14-day induction therapy with gefitinib at 250 mg daily. TRT was initiated on day 15 in 2-Gy fractions administered five times weekly to a total dose of 60 Gy. The primary end point of the study was the rate of treatment completion. Mutation status of the epidermal growth factor receptor gene (EGFR) was evaluated for patients with available tumor specimens. RESULTS: Nine eligible patients enrolled in the study received induction gefitinib monotherapy. Two patients were unable to begin TRT because of the development of progressive disease during the first 2 weeks of the protocol. Three of the remaining seven patients treated with gefitinib and concurrent TRT were unable to complete the planned treatment (two because of pulmonary toxicity and one because of progressive disease), and the study was therefore closed according to the protocol definition. Tumor samples were available for eight patients. EGFR mutations (deletion in exon 19) were detected in two patients, both of whom achieved a partial response and exhibited an overall survival of >5 years. CONCLUSIONS: Our results do not support further trials of gefitinib and TRT for unselected NSCLC patients. This therapeutic strategy may hold promise, however, for locally advanced NSCLC in patients with sensitizing EGFR mutations.
INTRODUCTION: A feasibility study was performed to examine the safety and toxicity profile of daily gefitinib (250 mg) administration with concurrent definitive thoracic radiation therapy (TRT) in patients with unresectable non-small cell lung cancer (NSCLC) of stage III. METHODS:Patients received a 14-day induction therapy with gefitinib at 250 mg daily. TRT was initiated on day 15 in 2-Gy fractions administered five times weekly to a total dose of 60 Gy. The primary end point of the study was the rate of treatment completion. Mutation status of the epidermal growth factor receptor gene (EGFR) was evaluated for patients with available tumor specimens. RESULTS: Nine eligible patients enrolled in the study received induction gefitinib monotherapy. Two patients were unable to begin TRT because of the development of progressive disease during the first 2 weeks of the protocol. Three of the remaining seven patients treated with gefitinib and concurrent TRT were unable to complete the planned treatment (two because of pulmonary toxicity and one because of progressive disease), and the study was therefore closed according to the protocol definition. Tumor samples were available for eight patients. EGFR mutations (deletion in exon 19) were detected in two patients, both of whom achieved a partial response and exhibited an overall survival of >5 years. CONCLUSIONS: Our results do not support further trials of gefitinib and TRT for unselected NSCLCpatients. This therapeutic strategy may hold promise, however, for locally advanced NSCLC in patients with sensitizing EGFR mutations.