Phase I trial of concurrent erlotinib, celecoxib, and reirradiation for recurrent head and neck cancer.

Abstract

5561 Background: Concurrent inhibition of EGFR and COX-2 has previously been shown to be an active and well tolerated regimen in recurrent head and neck cancer (Wirth, JCO 23: 6976, 2005). Based on robust preclinical data, we tested concurrent erlotinib and celecoxib as radiosensitizing agents. Methods: Patients with unresectable or high risk adjuvant (microscopic positive margins or extracapsular extension) head and neck cancer and M0 requiring reirradiation were eligible. Eligible patients received celecoxib (200 to 600 mg BID) and erlotinib (150 mg QD) starting 14 days prior to and concurrent with reirradiation (IMRT 60 to 72.4 Gy in 2.2 Gy QD M-F). The primary objective was to determine the safety, tolerability, and maximum tolerated (MTD) dose of celecoxib. The starting dose was celecoxib 200 mg BID escalated to 400 mg BID and 600 mg BID using a 3+3 design with an expanded cohort at the MTD. Results: Between 3/07 to 12/09, 15 pts were enrolled with a median follow-up of 10 months. Patient characteristics include median age 68 (6 age >75); 11 male; 10 with ECOG PS 2, 9 had unresectable disease, 3 with second primaries, 8 received prior chemotherapy and median prior RT dose was 62 Gy. There were no dose limiting toxicities (DLTs) in dose levels (DL) 1 and 2. Two of three patiens at DL3 developed DLTs consisting of gr 3 bone necrosis and trismus. Therefore, celecoxib 400 mg BID was declared the MTD with concurrent erlotinib and reirradiation. Overall gr ≥3 toxicities were uncommon and consisted of gr 3 mucositis (n=3), gr 3 dermatitis (n=2), and gr 3 pain (n=3). At last follow-up, five are alive with no evidence of disease (NED), three developed locoregional progression, three had distant progression, one had both local and distant progression and three are NED but succumbed to comorbid illness. Maintenance erlotinib 150 mg QD until progression was allowed but only 3 patients participated. Conclusions: Concurrent erlotinib, celecoxib and reirradiation is a well tolerated regimen that demonstrates activity in a difficult to treat population of previously irradiated patients. These data suggest that this regimen warrants further study particularly in patients who failed chemoradiation or elderly patients with PS 2. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Genentech, sanofi-aventis OSI, Pfizer