A Multicenter Evaluation of Different Chemotherapy Regimens in Older Adults With Head and Neck Squamous Cell Carcinoma Undergoing Definitive Chemoradiation
Alexander Rühle, M. Weymann, Max Behrens, Sebastian Marschner, Marlen Haderlein, Alexander Fabian, Carolin Senger, Daniel R. Dickstein, Johannes Kraft, Jens von der Grün, Eric Chen, Todd Aquino-Michaels, Justus Domschikowski, Amanda Bickel, Alev Altay-Langguth, Goda Kalinauskaitė, Victor Lewitzki, Marcelo Bonomi, Dukagjin Blakaj, Sachin R. Jhawar, Sujith Baliga, Rahul Barve, Konstantinos Ferentinos, Constantinos Zamboglou, Sören Schnellhardt, Erik Haehl, Simon K. B. Spohn, Thomas Kuhnt, Daniela Zöller, Matthias Gückenberger, Volker Budach, Claus Belka, Richard L. Bakst, Arnulf Mayer, Heinz Schmidberger, Anca-Ligia Grosu, Panagiotis Balermpas, Carmen Stromberger, Nils H. Nicolay
Abstract
PurposeThe 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 radiotherapy is considered standard regimen for patients with locoregionally advanced HNSCC, there is substantial real-world heterogeneity regarding concomitant chemotherapy in older HNSCC patients.MethodsThe XXX study is an international multicenter cohort study including older (≥65 years) HNSCC patients treated with definitive radiotherapy at 13 academic centers in the United States and Europe. Here, patients with concomitant chemoradiation were analyzed regarding overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier analyses, while Fine‐Gray competing risks regressions were performed regarding the incidence of locoregional failures (LRFs) and distant metastases (DMs).ResultsSix 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 (HR=1.39 [1.03-1.89], p<0.05) and a higher incidence of LRFs (SHR=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 multi-agent cisplatin regimens (all p>.05). 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), PFS (HR=0.66 [0.51-0.87], p=.003), and lower incidence of LRFs (SHR=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).ConclusionsSingle-agent cisplatin can be considered as the standard chemotherapy regimen for older HNSCC patients who can tolerate cisplatin. Cumulative cisplatin doses are prognostically relevant also in older HNSCC patients.Trial RegistrationXXX