Session Item

There is increasing evidence that specific subgroups of elderly patients with head-and-neck squamous cell carcinoma (HNSCC) may benefit from concurrent chemotherapy when treated with definitive radiotherapy. While three-weekly high-dose (100 mg/m2) cisplatin is generally considered the standard regimen for definitive chemoradiation, it may result in considerable toxicities in vulnerable older patients; therefore, alternative chemotherapy regimens may be more adequate. The aim of this large multicenter analysis was to examine the oncologic efficacy of different chemotherapy doses and protocols in elderly HNSCC patients.

A total of 677 older (≥65 years) patients with locoregionally advanced HNSCCs of the oral cavity, oropharynx, hypopharynx or larynx that received definitive chemoradiation between 2005 and 2019 at 12 tertiary cancer centers in Germany, Switzerland, Cyprus and the United States were included in this retrospective analysis. Overall survival (OS), progression-free survival (PFS) and locoregional control (LRC) were compared between the different chemotherapy protocols following a pre-registered study protocol (NCT05337631).

The median age was 71 years (interquartile range [IQR], 68-76 years), the median Charlson Comorbidity Index amounted to 1 point (IQR, 0-3), and 564 patients (83%) had an ECOG performance status of ≤1. One-hundred twenty-two patients (18%) exhibited an HPV-positive oropharyngeal carcinoma. Cisplatin (n=298, 44%; 147 [49%] of them receiving cisplatin 30-40 mg/m2 weekly), cisplatin/5-FU (n=137, 20%), carboplatin (n=68, 10%) and mitomycin C/5-FU (n=64, 9%) were the most commonly applied chemotherapy regimens. The median cisplatin dose of patients receiving single-agent cisplatin amounted to 175 mg/m2 (IQR, 120-200 mg/m2). Cisplatin doses of ≥200 mg were associated with significantly increased OS, PFS and LRC (all p<0.05, log-rank test) compared to cumulative doses <200 mg. Beyond 200 mg/m2, no additional benefit could be elucidated for higher cisplatin doses (p=0.067 for OS, p=0.095 for PFS, p=0.340 for LRC). There was no difference in terms of OS (p=0.135), PFS (p=0.523) or LRC (p=0.948) in patients receiving multi-agent chemotherapy compared to patients treated with cisplatin only. Carboplatin (±5-FU or docetaxel or paclitaxel) was associated with significantly diminished PFS (p<0.05) and LRC (p<0.05) in comparison to single-agent cisplatin regimens, while OS was comparable (p=0.597).

This analysis based on a multicenter study suggests that a minimum cumulative cisplatin dose of 200 mg/m2 should be pursued also in older adults with HNSCC undergoing definitive chemoradiation; however, there seems to be no or little benefit of higher doses beyond 200 mg/m2. There are indications of reduced efficacy of carboplatin compared to cisplatin regimens, suggesting that cisplatin should not be generally replaced by carboplatin in older cisplatin-eligible HNSCC patients.