Clinical Trials Group Study

To determine the phase II dose and objective response rate of erlotinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor, in combination with cisplatin in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC). Patients and Methods HNSCC patients with no prior chemotherapy and measurable disease were treated in three escalating-dose cohorts of daily continuous oral (PO) erlotinib and intermittent intravenous (IV) cisplatin given every 21 days. The recommended phase II dose (RPTD) was then evaluated in a two-stage trial with a primary end point of objective response rate. Results A total of 51 patients were enrolled. The RPTD was identified as erlotinib 100 mg PO daily and cisplatin 75 mg/m2 IV every 21 days. Forty-five patients were treated at the RPTD, of which 44 and 43 were eligible for toxicity and efficacy evaluations, respectively. The intention-to-treat response rate was 21%, with one complete and eight partial responses (95 % CI, 10 % to 36%), and disease stabilization was achieved in 21 patients (49%; 95 % CI, 33 % to 65%). Median progression-free survival was 3.3 months (95 % CI, 2.7 to 4.8 months) and median overall survival was 7.9 (95 % CI, 5.6 to 9.5) months. The combination was well tolerated, with minimal grade 3 or higher toxicity. Subgroup analysis suggested that patients who developed higher grade skin rashes during cycle 1 had better survival outcomes (P .034). Conclusion This schedule of erlotinib and cisplatin has a favorable toxicity profile and has antitumor activity in HNSCC comparable to standard combination chemotherapy regimens. J Clin Oncol 25:2178-2183. © 2007 by American Society of Clinical Oncolog