Phase II clinical trial of eribulin in advanced or recurrent cervical cancer (CC).

TPS5617 Background: Eribulin (E), a Halichondrin B analog from the marine sponge H. okadai shows anticancer effects via G2/M cell cycle arrest, mitotic spindle disruption, and apoptosis. E has efficacy in pretreated metastatic breast cancer (BC) patients (pts), and preclinical antitumor activity in squamous cell carcinoma (SCC) tumor models. Microtubules (MT) have a dynamic and critical role in cancer growth and metastasis. Increasing data support their role in endoplasmic reticulum stress (ERS) and the unfolded protein response. The glucose-regulated protein-78 (GRP78), a key regulator of the ERS response, is upregulated by taxane-chemotherapy (CT) and is associated with clinical outcome. Previous reports show that high GRP78 levels predict response to MT inhibitors (paclitaxel) in BC. Given the novel tubulin-specific mechanism of action of E and its activity in SCC, we conducted a 2-stage phase 2 study of E in pts with advanced/recurrent CC to examine the clinical activity and potential predictors of re...