Gefitinib plus concomitant boost accelerated radiation (AFX-CB) and concurrent weekly cisplatin for locally advanced unresectable squamous cell head and neck carcinomas (SCCHN): A phase II study

Abstract

6031 Background: Molecular inhibition of EGFR signaling represents one of the most promising current advances for the treatment of SCCHN. This study assesses the feasibility, toxicity and efficacy of gefitinib along with AFX-CB regimen and weekly cisplatin in treatment- naïve patients (pts) with locally advanced unresectable SCCHN. Methods: Eligible pts had stage III-IV SCCHN, exclusive of nasopharyngeal cancer. Tumors had to be considered unresectable by a multidisciplinary head/neck tumor board. AFX-CB dose was 72 Gy in 42 fractions over 6 weeks, delivered in 1 daily fraction of 1.8 Gy during the first 3.5 weeks and 2 fractions per day, 1.8 Gy and 1.5 Gy separated by a 6-hour interval, during the last 2.5 weeks. Cisplatin (40 mg/m2) was given weekly for the first 4 weeks. Gefitinib (250 mg PO OD) was started 1 day before radiochemotherapy (RCT) and continued 3 months after the end of AFX-CB. Response was evaluated 3 months after radiotherapy using RECIST criteria. Mucosal and skin toxicities were evaluated using the RTOG scale. Results: From Dec 2002 to Dec 2004, 46 pts with SCCHN, ECOG PS 0–1 and adequate hematologic and renal functions were included. Median age was 55 years (range, 39 to 75); T4, 73%; N2/3, 61%; stage IV disease, 93%. Four pts did not complete the concomitant treatment (1 PD/3 toxicity) and 8 pts did not complete the gefitinib monotherapy phase due to PD. Grade 3 and 4 toxicity was consistent with previous RCT or single agent gefitinib trials, and included mucositis (40% and 7%, respectively), radiation dermatitis (14% and 0%), skin rash (5% and 0%), and diarrhea (2% and 0%). Chemotherapy-associated toxicity was mild with only 2 cases of grade 3 neutropenia and 3 cases of grade 3 anaemia. Three months after AFX- CB, 24 pts (52%) achieved a complete remission, 5 pts (11%) a partial remission, and 17 pts (37%) were non-responders (SD, PD, and not evaluable). With a median follow-up of 23 months (range 1–43) 2-year PFS and OS are 47% and 56% respectively. Conclusions: The addition of gefitinib to radiochemotherapy appears tolerable and feasible. Efficacy is encouraging for this poor prognosis population, and further development of this targeted combined-modality paradigm is warranted. No significant financial relationships to disclose.