Gemcitabine-Based versus Fluoropyrimidine-Based Chemotherapy and Role of Platinum Combination for First-Line Palliative Systemic Treatment in Advanced Ampullary Adenocarcinoma

Purpose: Ampullary adenocarcinoma is a rare malignancy with limited evidence on the efficacy of systemic chemotherapy for advanced disease. This study aimed to evaluate the treatment outcomes of gemcitabine- and fluoropyrimidine-based regimens and the benefits of platinum combination therapy. Patients and Methods: This retrospective study reviewed the data of patients with advanced ampullary adenocarcinoma treated at a university hospital in Southern Thailand between 2005 and 2024. Results: Among the 97 patients, 71 (73.2%) received palliative chemotherapy, including 43 (60.6%) receiving gemcitabine-based regimens and 28 (39.4%) receiving fluoropyrimidine-based regimens. Median overall survival (OS) and progression-free survival (PFS) for gemcitabine-based vs. fluoropyrimidine-based regimens were 14.4 vs. 11.5 months (adjusted hazard ratio [HR] 0.85; 95% CI 0.34– 2.13; P = 0.725) and 8.67 vs. 7.18 months (adjusted HR 0.60; 95% CI 0.26– 1.36; P = 0.219), respectively. No significant difference in OS or PFS was observed between platinum combination and single-agent chemotherapy. The objective response rate (ORR) was 9.3% for gemcitabine-based therapy, 14.3% for fluoropyrimidine-based therapy, and 26.9% for platinum combination therapy, compared to 2.2% for monotherapy. Conclusion: Gemcitabine- and fluoropyrimidine-based regimens demonstrated comparable survival outcomes. Platinum-combination chemotherapy was associated with a higher ORR, but no significant OS or PFS benefit was observed. Therefore, platinum-combination regimens may be considered in selected patients requiring tumor shrinkage, and these findings should be interpreted as hypothesis-generating real-world evidence.