Concurrent chemoradiotherapy with cisplatin given once-a-week versus every-three weekly in head and neck squamous cell carcinoma: Non-inferior, equivalent, or superior?

Cisplatin-based concurrent chemoradiotherapy is the contemporary standard-of-care in curative-intent management of loco-regionally advanced head and neck squamous cell carcinoma. The most optimal dose-schedule of concurrent cisplatin remains debatable with widespread variability in clinical practice. High-quality evidence in favour of cisplatin-based chemoradiotherapy is largely based on high-dose cisplatin given as 100 mg/m2 every three-weekly for up to three cycles. However, such dosing is typically associated with high rates of significant acute hematological and renal toxicity prompting the need for alternative lesser toxic dose-schedules. Compliance to three doses of three-weekly high-dose cisplatin is reportedly suboptimal with nearly 40% of patients unable to receive the third cycle thereby achieving cumulative cisplatin dose of 200 mg/m2 which is generally regarded sufficient for beneficial anti-tumor effect. The most common alternative schedule is low-dose (20-50 mg/m2) cisplatin once-weekly during radiotherapy. Such low-dose weekly regimens have undergone less rigorous prospective evaluation versus RT alone but continue to be widely used in co-operative group trials and routine clinical practice. In the last decade, several small prospective randomized controlled trials have reported significantly lesser toxicity and comparable disease-related outcomes with low-dose weekly cisplatin. However, two recent randomized controlled trials have re-ignited the debate globally due to their contradictory results, inferences, and conclusions. Through this commentary, we critically appraise and summarize the existing evidence-base to inform contemporary clinical practice and guide future research. There is increasingly emerging evidence that chemoradiotherapy with once-weekly cisplatin is non-inferior to three-weekly cisplatin for disease-related outcomes in curative-intent management of loco-regionally advanced head and neck cancer.