Multiagent concurrent chemoradiotherapy (MACCRT) and gefitinib in locoregionally advanced head and neck squamous cell cancer (HNSCC).
6037 Background: In patients (pts) with stage III-IV HNSCC, MACCRT has led to excellent locoregional control. Distant metastases (DM) are now the most common cause of treatment failure. This phase II study tested whether the oral EGFR inhibitor gefitinib (G) added to our Cleveland Clinic MACCRT regimen would decrease DM and improve survival. METHODS: Between 4/03 and 9/07, 60 previously untreated pts with stage III-IV (M0) HNSCC, and a performance status of <1 were enrolled on this study. Pts received hyperfractionated radiation (72-74.4 Gy at 120cGy bid) and concurrent chemotherapy with cisplatin (20 mg/m2/day) and fluorouracil (1,000 mg/m2/day), both given as 96-hour continuous IV infusions during weeks 1 and 4. G 250 mg daily was begun on day 1 of the radiation and continued for 2 years. The results were retrospectively compared to our previous study of 44 pts treated with the same MACCRT regimen without G between 1/96 and 9/00. RESULTS: The study population included a preponderance of Caucasian (97%) males (88%) with stage IV (80%) oropharynx tumors (68%), and with a median age of 58 (range 24-75) years. Patient and tumor characteristics were similar to the non-G treated historical cohort. When comparing the G vs. non-G treated pts, acute toxicities including transient renal dysfunction (28% v. 5% p = 0.002) and all-cause re-hospitalization (83% v. 64%, p = 0.022) were worse. Myelosuppression was similar. G-specific toxicity included > grade 1 rash in 60% and diarrhea in 35%. There were 5 deaths during treatment in the G group v. one in the non-G group (p = 0.19). Only a projected 44% of pts will complete the 2-year course of G. With a median follow-up in this trial of 37 (range 13-64) months, 3-year Kaplan-Meier outcome estimates do not differ between the study and the historical cohorts. Local control without surgery is 80% v. 88% (p = 0.21), DM control is 86% v. 76% (p = 0.19), freedom from recurrence is 72% v. 71% (p = 0.79), and overall survival is 67% v. 68% (p = 0.63) respectively. CONCLUSIONS: The addition of G to our MACCRT regimen was difficult for pts to complete. It did not improve any measured outcome and was associated with increased toxicity when compared to historical controls. [Table: see text].
Rodriguez, CP; Adelstein, DJ; Saxton, JP; Rybicki, LA; Lorenz, RR; Wood, BG; Scharpf, J; Lee, WT; Ives, DI
Volume / Issue
Start / End Page
Pubmed Central ID
Electronic International Standard Serial Number (EISSN)