Arzoxifene as therapy for endometrial cancer.

Abstract

OBJECTIVE:

Arzoxifene, an orally active third-generation selective estrogen-receptor modulator (SERM), opposes the action of estrogen on the breast and endometrium but exerts an estrogen-agonist effect on bone and the lipid profile. Since this is an appealing combination for hormonal therapy of estrogen-related cancers, we initiated testing the potential of arzoxifene in women with treatment-refractory endometrial cancer.

METHODS:

Two phase I studies were conducted to evaluate the safety and pharmacokinetics of single and multiple doses of arzoxifene. In addition, two multi-institutional phase II trials have been completed on 100 women with metastatic or recurrent endometrial cancer.

RESULTS:

No serious adverse events were observed in the single-dose phase I study, the principal side effect being hot flashes in 5/15 healthy volunteers. In the second phase I study, conducted in 32 women with metastatic breast cancer, one patient had a serious, possibly drug-related adverse reaction (pulmonary embolism). The two multi-institutional trials demonstrated significant activity at 20 mg/day in patients with metastatic or recurrent endometrial cancer. Observed clinical response rates were 25 and 31%, with a median response duration of 19.3 and 13.9 months, respectively. Progression of the disease was stabilized in a substantial number of women. Toxicity was mild, except for two cases of pulmonary embolism that might have been drug related.

CONCLUSIONS:

Further investigation is warranted to verify these preliminary response rates and the clinical significance of the stable disease cases, to compare clinical outcomes with those in progestin-treated women, and to elucidate the mechanisms of SERM action in this disease.

• Authors: Thomas W Burke, Cheryl L Walker
• Journal: Gynecologic oncology (Gynecol Oncol) Vol. 90 Issue 2 Pt 2 Pg. S40-6 (Aug 2003) ISSN: 0090-8258 [Print] United States
• PMID: 12928005 (Publication Type: Journal Article, Review)

Chemical References

• Antineoplastic Agents, Hormonal
• Piperidines
• Selective Estrogen Receptor Modulators
• Thiophenes
• LY 353381

Topics

• Antineoplastic Agents, Hormonal (adverse effects, pharmacokinetics, therapeutic use)
• Clinical Trials, Phase I as Topic
• Clinical Trials, Phase II as Topic
• Endometrial Neoplasms (drug therapy, metabolism)
• Female
• Humans
• Multicenter Studies as Topic
• Piperidines (adverse effects, pharmacokinetics, therapeutic use)
• Selective Estrogen Receptor Modulators (adverse effects, pharmacokinetics, therapeutic use)
• Thiophenes (adverse effects, pharmacokinetics, therapeutic use)