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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Harrison, MR; Hahn, NM; Pili, R; Oh, WK; Hammers, H; Sweeney, C; Kim, K; Perlman, S; Arnott, J; Sidor, C; Wilding, G; Liu, G

Published Date

  • December 2011

Published In

Volume / Issue

  • 29 / 6

Start / End Page

  • 1465 - 1474

PubMed ID

  • 20499131

Pubmed Central ID

  • 20499131

Electronic International Standard Serial Number (EISSN)

  • 1573-0646

Digital Object Identifier (DOI)

  • 10.1007/s10637-010-9455-x

Language

  • eng

Conference Location

  • United States