A phase II evaluation of ixabepilone in the treatment of recurrent/persistent carcinosarcoma of the uterus, an NRG Oncology/Gynecologic Oncology Group study

Gynecol Oncol. 2017 Jan;144(1):101-106. doi: 10.1016/j.ygyno.2016.10.026. Epub 2016 Oct 28.

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/m2 as 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.

Conclusion: In this cohort of women, single agent ixabepilone showed modest but insufficient clinical activity.

Keywords: Carcinosarcoma; Ixabepilone.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Carcinosarcoma / chemistry
  • Carcinosarcoma / drug therapy*
  • Carcinosarcoma / radiotherapy
  • Disease Progression
  • Disease-Free Survival
  • Epothilones / adverse effects
  • Epothilones / therapeutic use*
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local / chemistry
  • Neoplasm Recurrence, Local / drug therapy*
  • Response Evaluation Criteria in Solid Tumors
  • Retreatment
  • Survival Rate
  • Tubulin / analysis
  • Tubulin Modulators / therapeutic use
  • Uterine Neoplasms / chemistry
  • Uterine Neoplasms / drug therapy*
  • Uterine Neoplasms / radiotherapy

Substances

  • Antineoplastic Agents
  • Epothilones
  • TUBB3 protein, human
  • Tubulin
  • Tubulin Modulators
  • ixabepilone