Abstract 3735: Increased efficacy with use of combination therapy of API 31510 and gemcitabine in the treatment of pancreatic cancer

Pancreatic Carcinoma is one of the deadliest types of cancers and certainly one that is most clinically difficult to manage given that most diagnoses occur in late-stage disease. Gemcitabine is among the few FDA approved drugs used alone and in combination with other antineoplastic agents for pancreatic cancer. API 31510, a novel intravenous formulation of Ubidecarone, induced superior cell death kinetics in pancreatic carcinoma cell line, MiaPaca alone or in combination with gemcitabine. In addition, the study employed an in vivo model of pancreatic cancer to assess the translation of the cell-based data of combination gemcitabine and API 31510. Animals were randomized into 4 groups of 30 rats each; group 1 received no treatment, group 2 received gemcitabine (150 mg/kg weekly for 3 weeks with one week rest), group 3 were injected with API 31510 (50 mg/kg daily), and group 4 received a combination of daily API 31510 (50kg/mg) and gemcitabine at the aforementioned regimen. The untreated group exhibited steep death rates, whereas in API 31510, gemcitabine alone and the combination of API 31510 resulted in prolongation of life. API 31510 alone had significantly greater impact than gemcitabine alone. Animals treated with gemcitabine + API 31510 exhibited prolonged survival and elicited long-term remission that was statistically significant compared to other groups. In addition, palpable tumors were decreased in the groups treated with API 31510, and to a greater degree, in those treated with gemcitabine in combination with API 31510. It is noteworthy that tumor histology demonstrated a hallmark disruption in tumor vasculature with use if API 31510. Taken together, these findings suggest that API 31510 offers a new approach to treatment and management of pancreatic cancer alone and combination with established chemotherapy regimens that include gemcitabine. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3735. doi:1538-7445.AM2012-3735