A phase II study of 2-methoxyestradiol (2ME2) NanoCrystal® dispersion (NCD) in patients with taxane-refractory, metastatic castrate-resistant prostate cancer (CRPC).

Abstract

PURPOSE:

2ME2 (Panzem®) is a non-estrogenic derivative of estradiol with antiproliferative and antiangiogenic activity. Preclinical data support antitumor activity in prostate cancer. This trial evaluated the efficacy of 2ME2 NCD in patients with taxane-refractory, metastatic CRPC.

EXPERIMENTAL DESIGN:

Patients with metastatic CRPC who had progressed on only one prior taxane-based regimen were eligible. All patients received 2ME2 NCD at 1,500 mg orally four times daily, repeated in 28 day cycles. The primary endpoint was progression-free survival at month 6, with a secondary endpoint of PSA response. An exploratory endpoint was metabolic response on FDG-PET imaging.

RESULTS:

A total of 50 pts was planned. The study was terminated after 21 pts when a futility analysis showed the primary endpoint was unlikely to be reached. The median number of cycles on study was 2 (range <1 to 12). Adverse events (AE) of grade ≥3 related to the study drug occurred in 7 unique patients (33%): elevations in liver function tests, fatigue or weakness, gastrointestinal hemorrhage, and hyponatremia. Paired FDG-PET scans were obtained for 11 pts. No metabolic responses were observed.

CONCLUSIONS:

2ME2 NCD did not appear to have clinically significant activity in this study. 2ME2 NCD was well-tolerated and showed some evidence of biologic activity. Given the aggressive biology in this taxane-refractory population, the potential benefit from a cytostatic agent like 2ME2 might better be realized in the pre-chemotherapy (or rising PSA only) stage of CRPC.

• Authors: Michael R Harrison, Noah M Hahn, Roberto Pili, William K Oh, Hans Hammers, Christopher Sweeney, Kyungmann Kim, Scott Perlman, Jamie Arnott, Carolyn Sidor, George Wilding, Glenn Liu
• Journal: Investigational new drugs (Invest New Drugs) Vol. 29 Issue 6 Pg. 1465-74 (Dec 2011) ISSN: 1573-0646 [Electronic] United States
• PMID: 20499131 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antineoplastic Agents
• Radiopharmaceuticals
• Fluorodeoxyglucose F18
• Estradiol
• 2-Methoxyestradiol

Topics

• 2-Methoxyestradiol
• Administration, Oral
• Aged
• Aged, 80 and over
• Antineoplastic Agents (administration & dosage, adverse effects, therapeutic use)
• Disease-Free Survival
• Estradiol (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
• Fluorodeoxyglucose F18
• Humans
• Male
• Middle Aged
• Nanoparticles
• Neoplasm Metastasis
• Positron-Emission Tomography (methods)
• Prostatic Neoplasms (drug therapy, pathology)
• Radiopharmaceuticals
• Treatment Outcome