A phase I/II study of weekly high-dose erlotinib in previously treated patients with nonsmall cell lung cancer

摘要: BACKGROUND. Preclinical studies have suggested that erlotinib at high doses may inhibit additional sites downstream of the epidermal growth factor receptor (EGFR), resulting in greater antitumor efficacy. The objective this study was to determine tolerability and efficacy high-dose administered on a weekly schedule patients with advanced nonsmall cell lung cancer (NSCLC). METHODS. The authors conducted Phase I/II trial progressive NSCLC who had received previous chemotherapy. In I portion, were enrolled 3-patient cohorts dose levels 1200 mg, 1600 2000 mg once weekly. II portion designed major response rate identified trial. RESULTS. Twenty-seven enrolled. No dose-limiting toxicity observed. Grade 1 2 rash diarrhea principle toxicities, each occurred 92% patients. Among 21 treated weekly, single identified, yielding 5% (95% confidence interval, 0.2–22%). For cohort, median survival 9.5 months. sole radiographic patient whose pretreatment tumor specimen harbored an EGFR exon 19 deletion. CONCLUSIONS. Erlotinib tolerated well by these NSCLC. did not reach stated interim analysis, prompting closure study. Cancer 2006. © 2006 American Society.