Multi-agent chemotherapy for refractory head and neck cancer

BACKGROUND: Recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) generally carries a poor prognosis. Although immunotherapies have improved outcomes for patients with high programmed death-ligand 1 (PD-L1) expression, treatment options remain poorly defined for those with low PD-L1 expression or those refractory to the EXTREME regimen (platinum-based chemotherapy plus cetuximab). To address this gap, we retrospectively evaluated the efficacy of the MEMOCLUB regimen (methotrexate, epirubicin, mitomycin-C, Oncovin, cisplatin, leucovorin, 5-fluorouracil, and bleomycin) for the treatment of platinum-refractory R/M HNSCC. METHODS: This retrospective cohort study, conducted at Taipei Veterans General Hospital, Taiwan, assessed the efficacy and safety of the MEMOCLUB chemotherapy regimen, administered with or without cetuximab, for platinum-refractory R/M HNSCC between 2015 and 2022. The study measured objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) according to the Response Evaluation Criteria in Solid Tumors 1.1 criteria. Statistical analyses were performed using Kaplan-Meier survival curves, log-rank tests, and the Cox proportional hazards model for identifying prognostic factors. RESULTS: A total of 124 patients were enrolled. The median PFS was 2.9 months and OS was 5.3 months. The ORR was 10.5%, with a corresponding disease control rate of 27.4%. In both univariate and multivariate analyses, cetuximab coadministration emerged as a significant prognostic factor for improved OS. Subgroup analysis revealed that cetuximab-naive patients derived the greatest survival benefit from the addition of cetuximab to the MEMOCLUB regimen. Hematological effects were the most common adverse events, with anemia being the most frequent. No cases of grade 3 or higher mucositis were reported. CONCLUSION: The MEMOCLUB regimen is a feasible salvage therapy in refractory HNSCC, which demonstrates reasonable efficacy and tolerability. The addition of cetuximab significantly prolonged survival in cetuximab-naive patients, suggesting that its coadministration is an advantageous strategy for this specific subgroup of platinum-refractory R/M HNSCC patients.