title: 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: OBJECTIVE
  The 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.
  
  
  METHODS
  Eligible women with unresectable uterine leiomyosarcoma progressing after prior cytotoxic therapy containing a taxane were treated with ixabepilone 40 mg/m(2) on day one of a 21 day 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).
  
  
  RESULTS
  Twenty-three of 26 women were evaluable (two wrong histology, one never treated) with two of 23 receiving 1 cycle of therapy. There were no complete or partial responses. Stable disease (SD) was seen in four patients (17.4%, median 3.4 months). Seventeen patients (73.9%) had increasing disease (PD) and two patients were inevaluable per RECIST. One patient had SD over 6 cycles of treatment. Median PFS for all 23 patients was 1.4 months and overall survival was 7.0 months. The predominant grade 3 or 4 toxicity was uncomplicated myelosuppression: neutropenia grade 3 (13%), grade 4 (17%), and anemia grade 3 (22%).
  
  
  CONCLUSIONS
  Ixabepilone as a single agent is not an active second-line therapy for uterine leiomyosarcoma previously treated with a taxane.
authors.affiliation: University of Virginia Health Systems, Division of Gynecology Oncology, P.O. Box 800712, Charlottesville, VA 22908, USA. Electronic address: lduska@virginia.edu.
authors.forename: Linda R
authors.initials: LR
authors.lastname: Duska
authors.affiliation: Gynecologic Oncology Group, Statistical & Data Center, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY 14263, USA. Electronic address: blessing@gogstats.org.
authors.forename: John A
authors.initials: JA
authors.lastname: Blessing
authors.affiliation: Rush-Presbyterian St. Luke's Medical Center, 1725 W. Harrison, Suite 842 Professional Bldg., Chicago, IL 60612, USA. Electronic address: jacob_rotmensch@rush.edu.
authors.forename: Jacob
authors.initials: J
authors.lastname: Rotmensch
authors.affiliation: The Peggy and Charles Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, 800 NE 10th Street, Oklahoma City, OK 73104, USA. Electronic address: Robert-mannel@ouhsc.edu.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Mannel
authors.affiliation: Hanjani Institute for Gynecologic Oncology, Abington Memorial Hospital, 1 Widener, 1200 Old York Road, Abington, PA 19001, USA. Electronic address: phanjani@amh.org.
authors.forename: Parviz
authors.initials: P
authors.lastname: Hanjani
authors.affiliation: Cleveland Clinic, 9500 Euclid Ave./A81, Cleveland, OH 44195, USA. Electronic address: rosep@ccf.org.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Rose
authors.affiliation: Massachusetts General Hospital, GYN Oncology, 55 Fruit St., Yawkey 9E, Boston, MA 02114, USA. Electronic address: ddizon@partners.org.
authors.forename: Don S
authors.initials: DS
authors.lastname: Dizon
mesh_terms: D000368:Aged; D034261:Epothilones / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007890:Leiomyosarcoma / Q000188:drug therapy*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D050257:Tubulin Modulators / Q000627:therapeutic use*; D014594:Uterine Neoplasms / Q000188:drug therapy*
chemical_list: D034261:Epothilones; D050257:Tubulin Modulators; C430592:ixabepilone
keywords: Ixabepilone; Uterine leiomyosarcoma
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