Phase 2 Clinical Trial Of Ixabepilone In Metastatic Cervical Carcinoma.

5593 Background: Ixabepilone is a microtubule-stabilizing agent approved for metastatic breast cancer. Preclinical data indicates activity in taxane-sensitive and resistant cells. Metastatic cervical carcinoma (mCC) has a poor prognosis and no accepted second line therapies. This study assessed the efficacy and safety of Ixabepilone in previously treated mCC. Methods: Patients with histologically confirmed mCC and at least one prior regimen received ixabepilone [6mg/m2/d X 5d] every 21 days. Primary endpoint was PFS by RECIST. Secondary endpoints were response rate, overall survival, and safety. We calculated the rate of tumor growth (g) as an additional efficacy measure. Results: Forty-one patients were enrolled; thirty four tumors were squamous. The median number of prior therapies was 2 (range1-6). Four patients (9.7%) had partial responses. Median time to progression in months was 2.3 for all, 3.84 for taxane-naive and 2.03 for taxane pre-treated patients (p=0.13). Consistent with this we found the rate of growth (g) in taxane-naive patients (0.0035/day) to be two-thirds the rate in taxane pre-treated patients (0.0053/day). Median overall survival (OS) was 5.84 months. Thirty-two patients discontinued treatment due to progression, two because of death, two for toxicity, and five for other reasons. The most frequent toxicities included vomiting (43%), sensory neuropathy (21%), and fatigue (60%). G3/4 toxicities were noted in 53% patients; all resolved without interventions Conclusions: Ixabepilone was well tolerated but showed very modest activity in second or higher line mCC. A trend to worse outcomes and a faster rate of growth was observed in taxane-pre-treated patients compared to taxane-naive patients. New strategies are needed for refractory mCC. Clinical trial information: NCT00924066.