An Exploration of Trifluridine/Tipiracil in Combination with Irinotecan in Patients with Pretreated Advanced Gastric Cancer

Abstract

Background: Trifluridine/tipiracil (FTD/TPI) and irinotecan are treatment options for heavily pretreated patients with advanced gastric cancer but with limited efficacies. We investigated the combination of FTD/TPI and irinotecan for such patients.Methods: Patients who refractory to fluoropyrimidine, platinum and taxane were enrolled into four cohorts (Level 1A/1B/2A/2B) used an escalated dose of irinotecan [100 (Level 1) or 125 mg/m2 (Level 2) on days 1 and 15] with 2 schedules of FTD/TPI 35 mg/m2/dose: twice daily, on days 1-5 and 8-12 (Level A) or on days 1-5 and days 15-19 (Level B) of a 28-day cycle. The primary and secondary objectives were determination of maximum tolerated dose, dose-limiting toxicities (DLTs), and recommended phase II dose (RP2D) , and evaluation of disease control rate (DCR), respectively. Results: Eleven patients were enrolled; 2 at Level 1A, 3 at Level 1B and 6 at Level 2B. DLTs occurred in 2/2 patient at Level 1A, and 2/6 patients at Level 2B. Grade 3 or higher treatment-related adverse events were neutropenia (90.9%), leukopenia (54.5%), anemia (45.5%) and febrile neutropenia (18.2%). One patient at Level 2B achieved partial response and the DCR was 72.7% (95% CI 39.0- 94.0%). The median progression-free survival and overall survival was 3.0 months (95% CI 0.92- not reached) and 10.2 months (95% CI 2.2- not reached), respectively.Conclusion: The RP2D of FTD/TPI combined with irinotecan was determined to be Level 1B with manageable hematologic toxicities and feasible non-hematologic toxicities. Further evaluation for its efficacy in the RP2D is necessary. Mini-abstract: A phases Ib study of trifluridine/tipiracil in combination with irinotecan for advanced gastric cancer determined the recommended dose with manageable hematologic toxicities and feasible non-hematologic toxicities.

Trifluridine/Tipiracil in the Real-World Management of Metastatic Gastric and Gastroesophageal Junction Cancers in Canada

“…Our understanding of FTD/TPI in metastatic gastric/gastroesophageal cancer will benefit from further characterization of the Canadian treatment landscape and data on treatment response, survival outcomes, and adverse events beyond the scope of compassionate use programs. The multinational uptake of FTD/TPI is accompanied by growing interest in the benefits of its administration in multiagent regimens and subsequent to immunotherapy [26,37,38]-practices that also merit additional exploration and research.…”