Modified Scheduling of Gemcitabine and Nab-paclitaxel Results in Increased Treatment Efficacy in Pancreatic Cancer
Ahmad Hegazi, Ryan Robb, BS, Terence Williams, MD, PhD
Abstract
Pancreatic cancer, while only the 10th most common cancer in the nation, has grown to possess the second highest mortality rate of all cancers as a result of its frequent metastasis. A commonly administered chemotherapy regimen used to combat these advanced or metastatic pancreatic cancer is Gemcitabine and nab-paclitaxel (Abraxane®). The current clinical approach to this regimen is the simultaneous administration of both drugs. However, we have previously shown Gemcitabine to upregulate Caveolin-1 (Cav-1), a protein involved in cellular uptake of nutrients such as albumin. Nab-paclitaxel is an albumin-bound chemotherapeutic, so we hypothesized that pre-treatment of cells with Gemcitabine followed by nab-paclitaxel treatment using altered scheduling could enhance the effectiveness of the treatment when compared to simultaneous administration.
Staining Cav-1 in cells revealed increasing Cav-1 expression and albumin uptake in a time-dependent fashion when tumor cells were treated with gemcitabine. In vivo models in athymic nude mice confirmed substantial reduction in tumor growth of altered scheduling through pre-treatment with gemcitabine on Day 1, followed by nab-paclitaxel on Day 3, compared with concurrent administration on Day 1. Ongoing studies are evaluating the induction of programmed cell death, the dependency of Cav-1, as well as the dependency of cell cycle specific effects on the improved efficacy of this scheduling regimen. This simple and alternative treatment regimen could potentially translate into better clinical outcomes for patients with pancreatic cancer, without changing the chemotherapeutic compounds currently administered in the clinic. A phase II trial is being designed on the basis of these preclinical studies.
Poster
Very interesting research. In your study did you find any evidence that extending the trial (increasing time between administration of the two drugs) past what you tested might result in a more effective treatment, or do you believe the increase in efficiency between administering the drugs at the same time vs. over the period of 24 hours vs. one day apart will taper off?