A prospective randomised controlled trial of concurrent chemoradiation versus concurrent chemoradiation along with gefitinib in locally advanced squamous cell carcinoma of head and neck

Background: The primary aim of the study was to find out whether addition of Gefitinib to standard cisplatin-based chemo-radiation can offer better treatment outcome at the cost of acceptable toxicities. Materials and Methods: Between January 2011 and June 2012, 64 patients were enrolled in the study following obtaining institutional ethical committee clearance and proper informed consent from the patients. Patients recruited were randomly allocated into a control arm (who received External Beam Radiotherapy with conventional 2 Gy/fraction, 5 days a week for 7 weeks up to total dose of 66 Gy along with concomitant injection cisplatin at the dose of 30 mg/m ² of body surface area on every week during radiation) and study arm (who received radiotherapy with 2 Gy/fraction, 5 days a week for 7 weeks up to total dose of 66 Gy, along with concomitant injection cisplatin at the dose of 30 mg/m ² of body surface area on every week during radiation, plus Tablet Gefitinib (250 mg/day orally) during the total duration of radiation treatment). However, only 61 patients (31 in the control arm and 30 in the study arm) were available for analysis. The two groups were comparable in terms of age distribution, sex distribution, performance status, stage, primary site and histological grade. Results: 29.03% patients achieved complete response (CR) in the control arm while 36.67% patients achieved CR in the study arm (CR), but the difference was not significant statistically (P = 0.5255). Total number of patients achieving overall response (CR + partial response) in control arm was 19 (61.29%) while it was 23 in the study arm (76.67%). However, the difference of overall response between the study arm and the control arm was not statistically significant (P = 0.1947). Disease free survival (DFS) rate at 1 year was 22.58% for the control arm and 33.33% for the study arm but it was not statistically significant (P = 0.515). Addition of Gefitinib to standard concurrent cisplatin-based chemoradiation was well-tolerated with no significant increase in acute skin or mucosal toxicity. There was no significant increase in late toxicities like subcutaneous tissue fibrosis and xerostomia in the study arm. The only acute toxicity that was significantly worse in the study arm was diarrhea. However, it could be managed easily with supportive measures and did not contribute to delay in completion of treatment. Conclusion: We can conclude that addition of Gefitinib to standard concurrent cisplatin based chemoradiation is well-tolerated, and in our study we found better overall response and DFS (at 1 year) with addition of Gefitinib to standard concurrent chemoradiation. However, these encouraging results did not reach the level of statistical significance. Larger studies involving much greater number of patients across multiple institutions are required to validate those encouraging results and clearly define the role of addition of Gefitinib to current standard of care in locally advanced squamous cell carcinoma of head and neck.