Superior Therapeutic Efficacy of Nanoparticle Albumin Bound Paclitaxel Over Cremophor-Bound Paclitaxel in Experimental Esophageal Adenocarcinoma

Abstract

Esophageal adenocarcinoma (EAC) is the fastest growing cancer in the western world and the overall 5 year survival rate of EAC is below 20%. Most patients with EAC present with locally advanced or widespread metastatic disease, where current treatment is largely ineffective. Therefore, new therapeutic approaches are urgently needed. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is a novel albumin-stabilized, cremophor-free and water soluble nanoparticle formulation of paclitaxel, and the potential role of nab-paclitaxel has not been tested yet in experimental EAC. Here we tested the antiproliferative and antitumor efficacy with survival advantage of nab-paclitaxel as monotherapy and in combinations in in-vitro, and in murine subcutaneous xenograft and peritoneal metastatic survival models of human EAC. Nab-paclitaxel significantly inhibited in-vitro cell proliferation with higher in-vivo antitumour efficacy and survival benefit compared to paclitaxel or carboplatin treatments both in mono- and combination therapies. Nab-paclitaxel treatment increased expression of mitotic-spindle associated phospho-stathmin, decreased expression of proliferative markers and enhanced apoptosis. This study demonstrates that nab-paclitaxel had stronger antiproliferative and antitumor activity in experimental EAC than the current standard chemotherapeutic agents which supports the rationale for its clinical use in EAC.