4 - A Retrospective Comparative Study of TAI with Raltitrexed, Irinotecan, and Oxaliplatin in Advanced Pancreatic Cancer Complicated by Obstructive Jaundice

Purpose: This study aims to investigate the efficacy and safety of a novel three-drug TAI regimen, in which raltitrexed replaces 5-FU/leucovorin and is combined with irinotecan and oxaliplatin, for the treatment of advanced pancreatic cancer patients with obstructive jaundice.

Materials and Methods: This retrospective study enrolled 72 patients with advanced pancreatic cancer and obstructive jaundice who underwent metallic biliary stent placement followed by TAI treatment. Participants were stratified into Group A (gemcitabine plus oxaliplatin) and Group B (raltitrexed combined with irinotecan and oxaliplatin). After 1:1 PSM to balance confounding factors, tumor response, SPT, OS, and treatment-related adverse events (AEs) were compared between groups. Tumor response was assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Kaplan-Meier analysis with log-rank testing was employed to compare SPT and OS, while AEs were graded according to Common Terminology Criteria for Adverse Events version 5.0.

Results: A total of 72 patients underwent 362 TAI sessions. The overall median SPT and OS were 8.75 months (95% CI 7.72-9.77) and 9.80 months (95% CI 9.05-10.54), respectively. After PSM, 23 patients were included in each group with balanced baseline characteristics. Survival analysis demonstrated that median OS was significantly better in Group B than in Group A (10.68 months vs. 9.04 months, p=0.034). However, no statistically significant differences were observed between the two groups in median SPT (8.02 months vs. 9.30 months, p=0.306), stent restenosis rate (21.7% vs. 34.8%, p=0.326), objective response rate (ORR: 13.0% vs. 17.4%, p=0.681), or disease control rate (DCR: 52.2% vs. 60.9%, p=0.552). Regarding safety, the incidence of grade 1~2 diarrhea was significantly higher in Group B than in Group A (p=0.009), without any other statistically significant differences in other AEs between the two groups.

Conclusion: The raltitrexed combined with irinotecan and oxaliplatin regimen demonstrated potential survival advantages over the gemcitabine plus oxaliplatin regimen in TAI chemotherapy for advanced pancreatic cancer patients with obstructive jaundice, while demonstrating a higher propensity for mild diarrhea (grade 1~2) without exacerbating severe toxicity (grade 3~4 AEs). This regimen provided a novel locoregional therapeutic strategy for advanced pancreatic cancer patients with hepatic impairment or contraindications to systemic chemotherapy.