Purpose Chemoradiation with cisplatin 100 mg/m2 given once every 3 weeks is the standard
of care in locally advanced head and neck squamous cell cancer (LAHNSCC). Increasingly,
low-dose once-a-week cisplatin is substituted because of perceived lower toxicity
and convenience. However, there is no level 1 evidence of comparable efficacy to cisplatin
once every 3 weeks. Patients and Methods In this phase III randomized trial, we assessed
the noninferiority of cisplatin 30 mg/m2 given once a week compared with cisplatin
100 mg/m2 given once every 3 weeks, both administered concurrently with curative intent
radiotherapy in patients with LAHNSCC. The primary end point was locoregional control
(LRC); secondary end points included toxicity, compliance, response, progression-free
survival, and overall survival. Results Between 2013 and 2017, we randomly assigned
300 patients, 150 to each arm. Two hundred seventy-nine patients (93%) received chemoradiotherapy
in the adjuvant setting. At a median follow-up of 22 months, the estimated cumulative
2-year LRC rate was 58.5% in the once-a-week arm and 73.1% in the once-every-3-weeks
arm, leading to an absolute difference of 14.6% (95% CI, 5.7% to 23.5%); P = .014;
hazard ratio (HR), 1.76 (95% CI, 1.11 to 2.79). Acute toxicities of grade 3 or higher
occurred in 71.6% of patients in the once-a-week arm and in 84.6% of patients in the
once-every-3-weeks arm ( P = .006). Estimated median progression-free survival in
the once-a-week arm was 17.7 months (95% CI, 0.42 to 35.05 months) and in the once-every-3-weeks
arm, 28.6 months (95% CI, 15.90 to 41.30 months); HR, 1.24 (95% CI, 0.89 to 1.73);
P = .21. Estimated median overall survival in the once-a-week arm was 39.5 months
and was not reached in the once-every-3-weeks arm (HR, 1.14 [95% CI, 0.79 to 1.65];
P = .48). Conclusion Once-every-3-weeks cisplatin at 100 mg/m2 resulted in superior
LRC, albeit with more toxicity, than did once-a-week cisplatin at 30 mg/m2, and should
remain the preferred chemoradiotherapy regimen for LAHNSCC in the adjuvant setting.