Three Weekly Versus Weekly Cisplatin: Comparison of two Different Chemotherapy Protocols with Concurrent Radiotherapy in Locally Advanced Head and Neck Cancer

Abstract
Introduction: Chemoradiotherapy (CRT) with concurrent cisplatin-based chemotherapy is the treatment of choice of locally advanced head and neck cancers (LAHNC), but the optimal regimen of cisplatin remains contentious. Though 3-weekly cisplatin is the recommended schedule, it is associated with severe adverse reactions. A lower dose weekly schedule is generally accepted to be more tolerable and is widely used in our country. Methodology: Our study retrospectively compares the 3-weekly and the weekly concurrent cisplatin schedules in patients of LAHNC treated with CRT. Patients were selected for either schedule based on the treating physician’s preference. The two schedules were compared for treatment-related toxicities, radiotherapy interruptions, cumulative cisplatin doses delivered and overall survival (OS) as well as disease-free survival (DFS) at 2 years. Results: In our study, 43 patients received the 3-weekly schedule while 40 received the weekly schedule. Age, gender, disease stage or site did not affect selection for either regimen, except cancers of the nasopharynx and salivary glands, who almost exclusively received the 3-weekly schedule (90.1%). Patients who received adjuvant CRT after radical surgery were more likely to receive the weekly schedule (66.7%) while patients treated with up-front CRT were more often given the 3-weekly schedule (57.6%). Overall, the 3-weekly arm was associated with more toxicities and treatment breaks, but was more successful in delivering an adequate cumulative dose of cisplatin and had a better OS and DFS at 2 years follow up compared to the weekly arm. It also appeared that treating physicians were more likely to withhold one or more of the weekly cycles to manage treatment toxicity which lead to inadequate cumulative dosing in a high (45%) percentage of patients. Conclusion: Our study reiterates that the 3-weekly cisplatin arm has a better outcome profile than the weekly cisplatin arm at the price of increased toxicity. Weekly schedules have lower toxicities but may not achieve outcomes equivalent to 3-weekly unless adequate cumulative doses are achieved. As our study is retrospective and non-randomized, selection bias may have affected our results.