A Phase II evaluation of ixabepilone (IND #59699, NSC #710428) in the treatment of recurrent or persistent leiomyosarcoma of the uterus: An NRG Oncology/Gynecologic Oncology Group Study

Abstract

ObjectiveThe combination of gemcitabine and docetaxel is the standard first-line therapy for recurrent or metastatic uterine leiomyosarcoma. There is no standard second-line therapy. Ixabepilone is a semi-synthetic analog of epothilone B that binds to the same site on beta tubulin as paclitaxel and may be a more potent polymerizer of tubulin. We sought to determine the activity of ixabepilone as a single agent as second-line treatment for patients with metastatic uterine leiomyosarcoma who had received taxane based therapy. MethodsEligible women with unresectable uterine leiomyosarcoma progressing after prior cytotoxic therapy containing a taxane were treated with ixabepilone 40mg/m2 on day one of a 21day cycle. Patients with prior pelvic radiation were treated without dose reduction. Response Evaluation Criteria in Solid Tumors (RECIST) response was assessed by computed tomography (CT). ResultsTwenty-three of 26 women were evaluable (two wrong histology, one never treated) with two of 23 receiving 1cycle of therapy. There were no complete or partial responses. Stable disease (SD) was seen in four patients (17.4%, median 3.4months). Seventeen patients (73.9%) had increasing disease (PD) and two patients were inevaluable per RECIST. One patient had SD over 6cycles of treatment. Median PFS for all 23 patients was 1.4months and overall survival was 7.0months. The predominant grade 3 or 4 toxicity was uncomplicated myelosuppression: neutropenia grade 3 (13%), grade 4 (17%), and anemia grade 3 (22%). ConclusionIxabepilone as a single agent is not an active second-line therapy for uterine leiomyosarcoma previously treated with a taxane.