Effectiveness of Gefitinib as additional Radiosensitizer to Conventional Chemoradiation for Locally advanced non-metastatic Squamous Cell Carcinoma of Head and Neck. Prospective interventional Randomized Controlled Study

Approximately 90% of head and neck squamous cell carcinoma (HNSCC) overexpress epidermal growth factor receptor (EGFR). EGFR plays a role in predict­ing and modulating the response of HNSCC patients to radiation. Cetuximab is established as potent radiosensitizer.  However data regarding use of tyrosine kinase inhibitors like gefitinib is limited. Aim of this study is to establish the radiosensitizer efficacy of daily gefitinib with concurrent chemoradiotherapy in patients with locally advanced non metastatic HNSCC (LAHNSCC). Between July, 2008 to October, 2011, 104 patients with LAHNSCC were randomized into two arms; in Arm A (experimental arm), patients received gefitinib (250 mg orally daily along with cisplatin based chemoradiation) and Arm B (control arm), patients received concurrent cisplatin based chemoradiation with Cisplatin dose of 100mg/m2 intravenous infusion given on Days 1 and 22 with conventional fractionated radiation of 60-66 Gray. Response assessments were done using RECIST and adverse events by NCI-CTCAE version 3. The median follow-up time was 26 months (range 2-35 months). There was statistical difference in overall response between the two arms (p value 0.041) in favour of gefitinib arm (n=48) with overall response (ORR=CR+PR) of 91.6 % versus 69.5% in conventional cisplatin chemoradiation (n=46). Disease Free Survival favored the Gefitinib arm with Log Rank p value of 0.008. Gefitinib arm resulted in more grade 2 and 3 dermatitis, mucositis and diarrheal events. Adding Gefitinib to conventional chemoradiation in treatment of LAHNSCC improves ORR and DFS, with an increase in incidence of manageable toxicity. Keywords: Chemoradiation, Gefitinib, Radiosensitizer