A Multicenter Evaluation of Different Chemotherapy Regimens in Older Adults With Head and Neck Squamous Cell Carcinoma Undergoing Definitive Chemoradiation

Purpose: The number of older adults with head and neck squamous cell carcinoma (HNSCC) is increasing, and treatment of these patients is challenging. Although cisplatin-based chemotherapy concomitantly with radiation therapy is considered the standard regimen for patients with locoregionally advanced HNSCC, there is substantial real-world heterogeneity regarding concomitant chemotherapy in older patients with HNSCC. Methods and Materials: The SENIOR study is an international multicenter cohort study including older patients (≥65 years) with HNSCC treated with definitive radiation therapy at 13 academic centers in the United States and Europe. Patients with concomitant chemoradiation were analyzed regarding overall survival (OS) and progression-free survival (PFS) via Kaplan-Meier analyses. Fine‐Gray competing risk regressions were performed regarding the incidence of locoregional failures and distant metastases. Results: Six hundred ninety-seven patients with a median age of 71 years were included in this analysis. Single-agent cisplatin was the most common chemotherapy regimen (n = 310; 44%), followed by cisplatin plus 5-fluorouracil (n = 137; 20%), carboplatin (n = 73; 10%), and mitomycin C plus 5-fluorouracil (n = 64; 9%). Carboplatin-based regimens were associated with diminished PFS (hazard ratio [HR], 1.39 [1.03-1.89]; P < .05) and a higher incidence of locoregional failures (subdistribution HR, 1.54 [1.00-2.38]; P = .05) compared with single-agent cisplatin, whereas OS (HR, 1.15 [0.80-1.65]; P = .46) was comparable. There were no oncological differences between single-agent and multiagent cisplatin regimens (all P > .05). The median cumulative dose of cisplatin was 180 mg/m² (IQR, 120-200 mg/m²). Cumulative cisplatin doses ≥200 mg/m² were associated with increased OS (HR, 0.71 [0.53-0.95]; P = .02), increased PFS (HR, 0.66 [0.51-0.87]; P = .003), and lower incidence of locoregional failures (subdistribution HR, 0.50 [0.31-0.80]; P = .004). Higher cumulative cisplatin doses remained an independent prognostic variable in the multivariate regression analysis for OS (HR, 0.996 [0.993-0.999]; P = .009). Conclusions: Single-agent cisplatin can be considered in the standard chemotherapy regimen for older patients with HNSCC who can tolerate cisplatin. Cumulative cisplatin doses are prognostically relevant in older patients with HNSCC.