Concurrent chemotherapy and external radiation therapy: An open label non-inferiority phase III randomized controlled trial of weekly versus three weekly cisplatin and radical radiotherapy in locally advanced head and neck squamous cell carcinoma: CONCERT trial

Abstract

Abstract Background LA-HNSCC is treated with concurrent chemo-radiation. Majority of guidelines recommend bolus Cisplatin in the dose of 100\xa0mg/m2 (on days 1, 22, and 43). The meta-analysis reported by MACH-NC group found a greater benefit for platinum-based chemotherapy as compared with other protocols. Multiple studies back this notion. Other options are weekly cisplatin (30-40\xa0mg/m2) or split course radiation and combination of DDP+5FU. Alternative dosing schedules (e.g., 30 to 40\xa0mg/m2 weekly, 6\xa0mg/m2 daily, or 20\xa0mg/m2 daily for five days weeks 1 and 5) are used because of improved patient tolerance and ease of administration. 30\xa0mg/m2 of weekly cisplatin has found to be inferior to 3 weekly 100\xa0mg/m2. Three weekly schedules is the benchmark for further trials. In practice many of physicians alternatively, use low dose. 40\xa0mg/m2 has been found superior to RT alone in a phase II randomized study. Whether 40\xa0mg/m2 weekly cisplatin is inferior to 100\xa0mg/m2 is not known. Based on our previous report and our long experience we are quite comfortable with weekly Cisplatin (in the dose of 40\xa0mg/m2), and hypothesize that weekly Cisplatin (40\xa0mg/m2) times 6-7 is non-inferior to 3 weekly Cisplatin 100\xa0mg/m2 times three (days 1,22,43). Trial design Multicentric Open labelled, non-inferiority randomized controlled phase III trial. Sample size was calculated expecting 60% LRC (loco-regional control) rate at 2 years in control arm, and 65% in experimental arm, with 80%power of study, alpha error 5%, non-inferiority margin of 10%. Based on these parameters each arm will require143 patients (including 10% lost to follow up/protocol violations etc.). Main Inclusion criteria: Newly diagnosed, chemo/radiotherapy naive, biopsy or cytology proven, locally advanced head and neck squamous cell carcinoma excluding nasopharyngeal carcinoma (stage III and IV without distant metastases). ARM A: Three weekly Cisplatin100\xa0mg/m2 (Day1, 22, 43) to be started on first day of radiation and given on days 1,22,43 ARM B: Weekly Cisplatin40mg/m2 times 6-7 Primary objective: Loco Regional Control Rate at 2 years. Clinical trial identification CTRI/2018/03/012422 release date 08/03/2018. Legal entity responsible for the study Atul Sharma. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.