A phase II trial of thalidomide in patients with refractory uterine carcinosarcoma and correlation with biomarkers of angiogenesis: a Gynecologic Oncology Group study

Gynecol Oncol. 2012 Nov;127(2):356-61. doi: 10.1016/j.ygyno.2012.07.095. Epub 2012 Jul 14.


Objectives: To evaluate the efficacy and adverse events of thalidomide in previously-treated, measurable, persistent or recurrent carcinosarcoma of the uterus, and to explore associations between angiogenic markers with patient demographics and clinical outcome.

Methods: Eligible, consenting patients were treated until disease progression or toxicity intervened with daily starting dose of 200 mg thalidomide/day that was increased by 200 mg every 2 weeks to a target dose of 1000 mg/day. Endpoints included progression-free survival (PFS)≥6 months (primary), toxicity, response, overall PFS and survival. Pre- and post-treatment plasma were evaluated for a panel of angiogenic biomarkers and assessed against clinical outcomes.

Results: Of 55 enrolled patients, 45 were evaluable for toxicity and survival. Two patients (4%; 90% CI 1-13%) experienced a partial response, and 8 (18%; 90% CI 9-30%) had PFS≥6 months. Median PFS was 1.9 months and median survival was 5.9 months. Grade 2-3 sensory neuropathy was noted in 6 patients, and 4, 3, and 3 patients experienced grade 3 sedation, fatigue, and constipation, respectively. Three patients had grade 4 adverse events (2 thromboembolic, 1 anemia). High pre-treatment VEGFA levels were associated with poorer PFS and survival.

Conclusions: Treatment with thalidomide met the protocol specified goal of prolonging PFS at 6 months. However, based on results with newer agents, the activity was insufficient to support further investigation. Association between pre-treatment VEGFA and prognosis in this population supports further evaluation of anti-angiogenic therapies in uterine carcinosarcoma.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / therapeutic use*
  • Angiogenic Proteins / blood*
  • Biomarkers, Tumor / blood*
  • Carcinosarcoma / blood
  • Carcinosarcoma / drug therapy*
  • Carcinosarcoma / mortality
  • Drug Administration Schedule
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Middle Aged
  • Survival Analysis
  • Thalidomide / therapeutic use*
  • Treatment Outcome
  • Uterine Neoplasms / blood
  • Uterine Neoplasms / drug therapy*
  • Uterine Neoplasms / mortality


  • Angiogenesis Inhibitors
  • Angiogenic Proteins
  • Biomarkers, Tumor
  • Thalidomide