Exploration of treatment after multiline chemotherapy in recurrent head and neck cancer: Case report.

RATIONALE: Treatment of recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) remains challenging, especially after resistance develops to conventional chemotherapy, radiotherapy, and targeted agents. Novel formulations, such as polymeric micellar paclitaxel (pm-Pac), which offer a Cremophor-free delivery system, warrant investigation in salvage settings to overcome resistance and improve outcomes. PATIENT CONCERNS: Two patients with locally advanced HNSCC experienced multiple disease recurrences following several surgical resections. Both had received prior taxane-based chemotherapy alongside radiotherapy, anti-EGFR therapy, and immunotherapy, yet developed progressive disease, highlighting the clinical dilemma of managing multiply relapsed, treatment-refractory HNSCC. DIAGNOSES: Both patients were diagnosed with R/M HNSCC, demonstrated low PD-L1 expression (TPS 2% and 3%, respectively), and negative EBER status. INTERVENTIONS: Following progression on multiple prior lines of therapy, both patients received salvage regimens containing pm-Pac in combination with platinum, fluorouracil, and either an immune checkpoint inhibitor (tislelizumab, case 1) or a tyrosine kinase inhibitor (lenvatinib, case 2). The treatment was administered for 6 cycles, followed by maintenance therapy. OUTCOMES: The pm-Pac-based combination therapy achieved significant tumor regression. In case 1 (ear canal primary), the target lesion was reduced by 43.1%, resulting in a progression-free survival (PFS) of 8.2 months. In case 2 (laryngeal primary), a 59.1% reduction was observed, with a PFS of approximately 11 months. Treatment was generally tolerable, with manageable grade 2 neutropenia as the primary adverse event. LESSONS: These 2 cases suggest that reintroducing paclitaxel in its novel polymeric micellar formulation, pm-Pac, within a combination regimen may overcome prior resistance and provide meaningful disease control in heavily pretreated R/M HNSCC patients. This approach represents a potentially viable salvage strategy, warranting further clinical investigation to confirm its efficacy and optimal integration into the treatment sequence for refractory HNSCC.