A phase II trial of arzoxifene, a selective estrogen response modulator, in patients with recurrent or advanced endometrial cancer.

Abstract

OBJECTIVES:

The goal of this study was to determine response rate and evaluate toxicity of LY353381 (arzoxifene) in patients with recurrent or advanced endometrial cancer (EC).

METHODS:

A phase II, open-labeled study with arzoxifene was performed at 13 centers. Patients with measurable recurrent/advanced EC not amenable to curative therapies were eligible if either the primary tumor or recurrent tumor was ER+ and/or PR+. If receptor status could not be determined, patients with well or moderately well-differentiated EC were also permitted. Prior use of salvage chemotherapy was not allowed; however, prior use of progestagens was permitted and patients were stratified by prior exposure to progestagen. Patients received 20 mg/day PO, and were treated for at least 8 weeks in the absence of disease progression or unacceptable toxicity. Efficacy was based on the frequency of complete (CR) and partial (PR) responses, and a 95% confidence interval (CI) was calculated. The Kaplan-Meier method was used to analyze time to progression and duration of response.

RESULTS:

From February 1999 through April 2001, 37 patients were entered of whom 34 received treatment. Efficacy was evaluated for the 29 patients who received at least 4 weeks of therapy and at least one tumor response assessment. Safety was assessed in all 34 patients who received any drug. Thirty patients were defined as progestagen sensitive, and 4 patients were defined as progestagen failures. Twenty-six patients were ER+, and 22 were PR+. Nine (1 CR + 8 PR) of 29 patients responded (31%, CI 25-51%), with a median duration of response of 13.9 months. All 9 responses occurred in progestagen-sensitive patients. Two additional patients (one from each progestagen cohort) had stable disease for >or=6 months. The median progression-free interval was 3.7 months (CI 1.9-6.6 months) for all 29 patients. Toxicity was minimal with no grade 3-4 toxic effects, and 9 patients had only grade 1-2 toxic effects (7 grade 1, 2 grade 2). Hot flashes were the most common toxic effect and, in all 3 reported cases, were grade 1.

CONCLUSIONS:

Arzoxifene has demonstrated a high response rate with the longest median duration of response reported in a phase II trial of this patient population. The ease of administration and extremely favorable toxicity profile make this an agent warranting further evaluation.

• Authors: D Scott McMeekin, Alan Gordon, Jeffrey Fowler, Allen Melemed, Richard Buller, Thomas Burke, Jeffery Bloss, Paul Sabbatini
• Journal: Gynecologic oncology (Gynecol Oncol) Vol. 90 Issue 1 Pg. 64-9 (Jul 2003) ISSN: 0090-8258 [Print] United States
• PMID: 12821343 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

• Piperidines
• Selective Estrogen Receptor Modulators
• Thiophenes
• LY 353381

Topics

• Adult
• Aged
• Aged, 80 and over
• Disease-Free Survival
• Endometrial Neoplasms (blood, drug therapy)
• Female
• Humans
• Middle Aged
• Neoplasm Recurrence, Local (blood, drug therapy)
• Piperidines (blood, therapeutic use)
• Selective Estrogen Receptor Modulators (therapeutic use)
• Thiophenes (blood, therapeutic use)