Synergy Of Water Soluble Prodrug Triptolide (Minnelide) With Gemcitabine And Nab-Paclitaxel In Pancreatic Cancer.

259 Background: Gemcitabine with nab-paclitaxel is the standard of care for metastatic Pancreatic Ductal Adenocarcinoma (PDAC). Addition of nab-paclitaxel to gemcitabine improves the survival of patients with metastatic pancreatic cancer by only 6 weeks while increasing toxicity. Meaningful combinations that reduce the doses while improving efficacy are required. Water soluble prodrug of triptolide (Minnelide) is effective against PDAC in preclinical studies and has demonstrated activity in the ongoing phase I trial. We have evaluated the combination of low dose triptolide prodrug with lowered doses of Abraxane and gemcitabine in PDAC. Methods: Pancreatic cancer cell lines S2-013 and S2-VP10 were xenografted both subcutaneously as well as orthotopically in athymic nude mice. Efficacy of a combination of triptolide prodrug (Minnelide: 0.21mg/kg) with reduced dose of gemcitabine 100mg/kg + Abraxane 10mg/kg (~40% of the clinically effective dose) was evaluated and compared with both standard of care gemcitab...