Oral fixed-dose cyclophosphamide and capecitabine combination: A novel therapeutic approach in advanced head and neck cancer.

Abstract

e18013 Background: The treatment landscape for HNSCC is fraught with challenges stemming from late diagnoses, limited treatment access, and reduced tolerability due to socioeconomic factors. Mere 10-30% of cases are operable upon initial presentation, with majority presenting at advanced stages or experiencing disease recurrence. However, the accessibility of advanced therapies like those validated in EXTREME and KEYNOTE-048 trials remains contentious in India due to logistical and financial barriers. Thus need of the hour is innovative, economically viable, easily available and tolerable therapeutic options -fixed drug dose combination. Methods: This study focuses on evaluating the efficacy and safety of the capecitabine cyclophosphamide regimen in patients with advanced and metastatic HNSCC. The study conducted between June 2023 and Jan 2025 enrolled 123 patients, evaluating progression-free survival (PFS), overall survival (OS) and toxicity profiles. Patients included were adults with histologically confirmed HNSCC, deemed ineligible for intravenous (IV) chemotherapy due to poor performance status or patient preference. The treatment regimen consisted of oral capecitabine 2000 mg and cyclophosphamide 100 mg, administered orally for 14 days in 3-week cycles, up to a maximum of 6 cycles. Results: 123 patients were enrolled, with 2 patients lost to follow-up. ECOG performance status ranged from 0 to 1. The median age of the patients was 55yrs (27-80). The male-to-female ratio was 3.3:1. Most patients, 62.6%, were smokers, and 88.9% were tobacco consumers. Primary sites were as follows: oral cavity in 77 patients (63.6%), oropharynx in 15 patients (12.3%), larynx in 20 patients (16.5%), and hypopharynx in 9 patients (7.4%).Previous treatment was received by 81 patients (66.9%) and previous platinum by 70 patients (57.9%). The indication for palliative intent was metastatic disease in 26 patients(21.5%) and advanced disease in the rest 95 patients(78.5%). Among the advanced disease population 60% of patients had relapsed disease. The median PFS of 140 days and a median OS of 172 days. Importantly, no grade 3 or 4 AEs were reported, with the majority being manageable grade 1 mucositis. Conclusions: The PFS results are encouraging and at par with the currently available options of oral chemotherapy. Noteworthy, this benefit was seen irrespective of majority patients of oral cavity site and platinum refractory disease, known poor prognostic factors. The affordability, accessibility, and outpatient suitability make it a promising alternative to conventional chemotherapy regimens, particularly for patients in rural and underserved areas. Our study is the first report on the feasibility-safety and efficacy of a fixed drug dose combination of cyclophosphamide and capecitabine in advanced HNSCC.