Neoadjuvant Capecitabine in Advanced Cutaneous Squamous Cell Carcinoma of the Head and Neck

The incidence of cutaneous squamous cell carcinoma of the head and neck (cSCCHN) has increased, including among those with high-risk disease. Delays to access and initiation of care are associated with disease progression and worse outcomes. Capecitabine has previously been shown to be effective antitumor activity with low toxic effects.

To evaluate the efficacy and tolerability of neoadjuvant capecitabine (NC) in advanced cSCCHN by evaluating the clinical and pathologic stage migration.

This prospective case series was conducted from January 2024 to September 2025 at 2 academic centers in Montreal, Canada, and included consecutive patients with advanced cSCCHN who were awaiting surgery. The data were analyzed in November 2025.

Two cycles of NC (1000 mg, twice daily, on days 1-14, followed by a 1-week rest period) were administered according to the Capecitabine Prior to Tumor Resection in ENT Oncology (CAPTURE) protocol, with surgical resection performed within 1 to 2 weeks after treatment completion.

Clinical tumor response and clinical to pathologic stage migration, defined as the comparison of initial clinical stage with the postsurgical pathologic stage.

The mean (SD) age of the cohort of 15 patients was 77 (8.1) years; 6 patients (40%) were female, and 9 patients (60%) were male. Clinical tumor regression was observed in 10 of 15 patients (67%). Among those who underwent resection, 5 (42%) achieved a complete pathologic response. Two patients avoided surgery due to complete treatment response and opted to receive radiotherapy. Nonresponse occurred for 5 patients, including 1 patient who experienced progression to metastatic disease. No grade 3 or higher capecitabine-related toxic effects were reported.

This case series found that NC demonstrated significant tumor regression and pathologic response without severe treatment-related toxic effects. NC may be an effective treatment option for providing disease control and tumor downstaging in patients with advanced cSCCHN.