Neoadjuvant capecitabine in advanced cutaneous squamous cell carcinoma of the head and neck: prospective case series

The incidence of cutaneous squamous cell carcinoma of the head and neck (cSCCHN) has increased, including among those with high-risk disease. Capecitabine has previously been shown to have effective antitumor activity with low toxic effects. A prospective case series at two academic centers in Montreal, Canada, evaluated the efficacy and tolerability of neoadjuvant capecitabine (NC) among 15 consecutive patients awaiting surgery for advanced cSCCHN from January 2024 to September 2025. Patients received two cycles of NC (1000 mg twice daily on days 1-14 followed by a 1-week rest period), with surgical resection performed within 1 to 2 weeks after treatment completion. Main outcomes were clinical tumor response and clinical to pathological stage migration, defined as the comparison of initial clinical stage with the postsurgical clinical stage. 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 in 5 patients, including one patient who experienced progression to metastatic disease. No grade 3 or higher capecitabine-related toxic effects were reported. The authors conclude that NC demonstrated significant tumor regression and pathologic response without severe treatment-related toxic effects.