Phase 2 trial of aromatase inhibition with letrozole in patients with uterine leiomyosarcomas expressing estrogen and/or progesterone receptors

Cancer. 2014 Mar 1;120(5):738-43. doi: 10.1002/cncr.28476. Epub 2013 Nov 12.

Abstract

Background: Advanced uterine leiomyosarcoma (ULMS) is an incurable disease. A significant percentage of cases of ULMS express estrogen and/or progesterone receptors (ER and/or PR). To the authors' knowledge, the role of estrogen suppression in disease management is not known.

Methods: The authors performed a single-arm phase 2 study of the aromatase inhibitor letrozole at a dose of 2.5 mg daily in patients with unresectable ULMS with ER and/or PR expression confirmed by immunohistochemistry. Tumor assessments were performed at baseline, 6 weeks, 12 weeks, and every 8 weeks thereafter. Toxicity was monitored throughout treatment. The primary endpoint was the progression-free survival at 12 weeks.

Results: A total of 27 patients was accrued, with a median of 2 prior treatment regimens (range, 0-9 treatment regimens). The median duration of protocol treatment was 2.2 months (range, 0.4 months-9.9 months). The 12-week progression-free survival rate was 50% (90% confidence interval, 30%-67%). The best response was stable disease in 14 patients (54%; 90% CI, 36%-71%). Three patients, all of whom had tumors expressing ER and PR in > 90% of tumor cells, continued to receive letrozole for > 24 weeks. The most common reason for treatment discontinuation was disease progression (85%). Letrozole was found to be well tolerated.

Conclusions: Letrozole met protocol-defined criteria as an agent with activity in patients with advanced ULMS. Patients with the longest progression-free survival rate were those whose tumors strongly and diffusely expressed ER and PR.

Keywords: aromatase inhibitor; leiomyosarcoma; letrozole; phase 2 clinical trial.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Aromatase Inhibitors / administration & dosage
  • Aromatase Inhibitors / adverse effects
  • Aromatase Inhibitors / therapeutic use*
  • Disease-Free Survival
  • Drug Administration Schedule
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Leiomyosarcoma / drug therapy*
  • Leiomyosarcoma / metabolism
  • Letrozole
  • Middle Aged
  • Nitriles / administration & dosage
  • Nitriles / adverse effects
  • Nitriles / therapeutic use*
  • Proportional Hazards Models
  • Prospective Studies
  • Receptors, Estrogen / metabolism*
  • Receptors, Progesterone / metabolism*
  • Treatment Outcome
  • Triazoles / administration & dosage
  • Triazoles / adverse effects
  • Triazoles / therapeutic use*
  • Uterine Neoplasms / drug therapy*
  • Uterine Neoplasms / metabolism

Substances

  • Antineoplastic Agents
  • Aromatase Inhibitors
  • Nitriles
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Triazoles
  • Letrozole