Abstract 4522: Old dog, new tricks: The role of capecitabine in HPV-negative head and neck cancer

Abstract Objective: Treatment for HPV-negative head and neck squamous cell carcinoma (HNSCC) has seen little innovation, particularly in advanced-stage disease, where outcomes remain suboptimal. The public healthcare system's delays in access to care can exacerbate this issue, allowing tumors to progress prior to treatment initiation. This study explores the use of capecitabine, an oral chemotherapy agent, in both preoperative and recurrent settings for HPV-negative HNSCC. Study Design: We conducted a prospective cohort study of patients with stage III/IV HPV-negative HNSCC at two academic centers in Montreal, Canada. The study evaluated clinical and pathological responses in patients receiving capecitabine in a preoperative setting, with radiological and clinical outcomes assessed for those with unresectable recurrent disease. Results: Among the 34 patients included in the study (23 oral cavity, 1 oropharynx, 5 skin, 5 larynx), 31 received capecitabine preoperatively, while 3 had recurrent, unresectable disease. Of the 31 patients undergoing surgery, 16 exhibited clinical tumor reduction, 13 remained stable, and 2 experienced tumor growth. Pathological responses were observed in 15 patients, including 1 complete response (skin) and 6 major responses based on the modified Ryan criteria. Two non-responders developed recurrences within one year. The mean follow-up for surgical patients was 6 months. In the non-surgical cohort, all three patients showed reduced pain and radiological improvements, with a mean follow-up of 8 months. No significant toxicity related to capecitabine was reported. Conclusion: Capecitabine, used either in a preoperative window of opportunity or in the recurrent setting, demonstrated measurable clinical and pathological responses in patients with HPV-negative HNSCC. Given its efficacy and low toxicity, further investigation of this oral agent is warranted, particularly in resource-constrained settings where timely access to treatment may be a challenge. Citation Format: Marco Antonio Mascarella, Nisha Suarez, Keith Richardson, Alex Mlynarek, Michael Hier, Nader Sadeghi, Khalil Sultanem, Derin Caglar, Marc Pusztaszeri, Livia Florianova, Nathaniel Bouganim, Khashayar Esfahani. Old dog, new tricks: The role of capecitabine in HPV-negative head and neck cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4522.