title: A phase II evaluation of ixabepilone in the treatment of recurrent/persistent carcinosarcoma of the uterus, an NRG Oncology/Gynecologic Oncology Group study.
abstract: BACKGROUND
  The primary objectives were to determine the objective response rate (ORR) and safety profile of ixabepilone in women with recurrent or persistent uterine carcinosarcoma (UCS). Secondary objectives included progression-free survival (PFS) and overall survival (OS). Exploratory translational objectives included characterization of class III beta tubulin expression and its association with response, PFS, and OS.
  
  
  METHODS
  Patients had measurable disease; up to two prior chemotherapeutic regimens were allowed, but must have included a taxane. Women received ixabepilone 40mg/m2as a 3hour IV infusion on day 1 of a 21daycycle. Treatment was continued until disease progression or unacceptable toxicity occurred.
  
  
  RESULTS
  Forty-two women were enrolled, with 34 eligible and evaluable. Median age was 68years. ECOG performance status was 0 in 56% of women, 38% had received radiation, and 15% had received 2 lines of chemotherapy. Overall ORR was 11.8% (4/34, 90% CI 4.2-25.1%); all were partial responses. Stable disease for at least 8weeks was achieved in 8 patients (23.5%). Median PFS and OS were 1.7mo and 7.7mo, respectively, with a median follow-up of 37mo. Six month PFS was 20.6%. Major grade≥3 toxicities were neutropenia (47%), fatigue (15%), dehydration (15%), hypertension (15%), and hyponatremia (15%); grade 2 peripheral neuropathy was reported in 18%. In this small sample size, class III beta tubulin expression in the primary tumor was not associated with the response to ixabepilone, PFS, or OS.
  
  
  CONCLUSIONS
  In this cohort of women, single agent ixabepilone showed modest but insufficient clinical activity.
authors.affiliation: Dept. of Gynecologic Oncology, Washington University School of Medicine, Saint Louis, MO 63110, United States. Electronic address: mccourtc@wudosis.wustl.edu.
authors.forename: Carolyn K
authors.initials: CK
authors.lastname: McCourt
authors.affiliation: NRG Oncology Statistics & Data Management Center, Roswell Park Cancer Institute, Buffalo, NY 14263, United States. Electronic address: wdeng@gogstats.org.
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.affiliation: Dept. of Gynecologic Oncology, Massachusetts General Hospital Cancer Center, Boston, MA 02114, United States. Electronic address: ddizon@mgh.harvard.edu.
authors.forename: Don S
authors.initials: DS
authors.lastname: Dizon
authors.affiliation: NRG Oncology Statistics & Data Management Center, Roswell Park Cancer Institute, Buffalo, NY 14263, United States. Electronic address: hlankes@gogstats.org.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Lankes
authors.affiliation: Dept. of Gynecologic Oncology, Massachusetts General Hospital Cancer Center, Boston, MA 02114, United States. Electronic address: mbirrer@partners.org.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Birrer
authors.affiliation: Dept. of Pathology, Women & Infants Hospital of Rhode Island, Providence, RI 02905, United States. Electronic address: mlomme@wihri.org.
authors.forename: Michele M
authors.initials: MM
authors.lastname: Lomme
authors.affiliation: Dept. of Obstetrics & Gynecology, Washington University School of Medicine, Saint Louis, MO 63110, United States. Electronic address: mpowell@wustl.edu.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Powell
authors.affiliation: Dept. of Gynecologic Oncology, Florida Hospital Cancer Institute CCOP, Orlando, FL 32804, United States. Electronic address: tkendrick2@gmail.com.
authors.forename: James E
authors.initials: JE
authors.lastname: Kendrick
authors.affiliation: Dept. of Oncology & Hematology, Lake University Ireland Cancer Center, Mentor, OH 44060, United States. Electronic address: Joel.Saltzman@uhhospitals.org.
authors.forename: Joel N
authors.initials: JN
authors.lastname: Saltzman
authors.affiliation: Dept. of Gynecologic Oncology, Cooper Health, Camden, NJ 08103, United States. Electronic address: warshal-david@cooperhealth.edu.
authors.forename: David
authors.initials: D
authors.lastname: Warshal
authors.affiliation: Section of Gynecologic Oncology, University of Chicago, Chicago, IL 60637, United States. Electronic address: meaghan.tenney@northside.com.
authors.forename: Meaghan E
authors.initials: ME
authors.lastname: Tenney
authors.affiliation: Dept. of Gynecologic Oncology, University of Wisconsin-Madison, Madison, WI 53792, United States. Electronic address: dmkushner@wisc.edu.
authors.forename: David M
authors.initials: DM
authors.lastname: Kushner
authors.affiliation: Dept. of Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, United States. Electronic address: aghajanc@mskcc.org.
authors.forename: Carol
authors.initials: C
authors.lastname: Aghajanian
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002296:Carcinosarcoma / Q000737:chemistry / Q000188:drug therapy* / Q000532:radiotherapy; D018450:Disease Progression; D018572:Disease-Free Survival; D034261:Epothilones / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000737:chemistry / Q000188:drug therapy*; D066066:Response Evaluation Criteria in Solid Tumors; D019233:Retreatment; D015996:Survival Rate; D014404:Tubulin / Q000032:analysis; D050257:Tubulin Modulators / Q000627:therapeutic use; D014594:Uterine Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000532:radiotherapy
chemical_list: D000970:Antineoplastic Agents; D034261:Epothilones; C498585:TUBB3 protein, human; D014404:Tubulin; D050257:Tubulin Modulators; C430592:ixabepilone
keywords: Carcinosarcoma; Ixabepilone