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

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Summary

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.

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Acknowledgements

We thank our patients and their families for their participation in this study. Special thanks to the investigators and staff of the Genitourinary Program at the University of Wisconsin Carbone Cancer Center, Indiana University Simon Cancer Center, Johns Hopkins Kimmel Comprehensive Cancer Center, and Dana-Farber Cancer Institute.

Grant Support

EntreMed, Inc. (sponsor/funding); Department of Defense Prostate Cancer Clinical Trial Consortium Award (P30 CA14520); Prostate Cancer Foundation Therapy Consortium.

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Authors and Affiliations

  1. University of Wisconsin Carbone Cancer Center, WIMR Room 7131, 1111 Highland Avenue, Madison, WI, 53705, USA

    Michael R. Harrison

  2. Indiana University Simon Cancer Center, Indianapolis, IN, USA

    Noah M. Hahn

  3. Roswell Park Cancer Institute, Buffalo, NY, USA

    Roberto Pili

  4. Mount Sinai Medical Center, Tisch Cancer Institute, New York, NY, USA

    William K. Oh

  5. Johns Hopkins Kimmel Cancer Center, Baltimore, MD, USA

    Hans Hammers

  6. Dana-Farber Cancer Institute, Boston, MA, USA

    Christopher Sweeney

  7. University of Wisconsin Carbone Cancer Center, Madison, WI, USA

    KyungMann Kim, Scott Perlman, George Wilding & Glenn Liu

  8. EntreMed, Inc., Rockville, MD, USA

    Jamie Arnott & Carolyn Sidor

  9. University of Wisconsin Translational Imaging Research (TIR) Group, Madison, WI, USA

    Michael R. Harrison, Scott Perlman & Glenn Liu

  10. Department of Defense Prostate Cancer Clinical Trials Consortium, New York, NY, USA

    Michael R. Harrison, Hans Hammers, Christopher Sweeney, KyungMann Kim, George Wilding & Glenn Liu

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Correspondence to Michael R. Harrison.

Additional information

ClinicalTrials.gov Identifier: NCT00394810.

Prior Presentations: ASCO 2008 Annual Meeting, abstract 5173.

This clinical research article is original work and has not been published or submitted elsewhere.

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Harrison, M.R., Hahn, N.M., Pili, R. et al. A phase II study of 2-methoxyestradiol (2ME2) NanoCrystal® dispersion (NCD) in patients with taxane-refractory, metastatic castrate-resistant prostate cancer (CRPC). Invest New Drugs 29, 1465–1474 (2011). https://doi.org/10.1007/s10637-010-9455-x

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