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

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

Research output: Contribution to journalArticle

54 Citations (Scopus)

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-PETscans 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.

Original languageEnglish (US)
Pages (from-to)1465-1474
Number of pages10
JournalInvestigational New Drugs
Volume29
Issue number6
DOIs
StatePublished - Dec 2011
Externally publishedYes

Fingerprint

Nanoparticles
Prostatic Neoplasms
Medical Futility
Gastrointestinal Hemorrhage
Hyponatremia
Liver Function Tests
Cytostatic Agents
Disease-Free Survival
Fatigue
Estradiol
Research Design
Drug Therapy
2-methoxyestradiol
taxane
Pharmaceutical Preparations
Population

Keywords

  • Antiangiogenesis
  • Antiproliferative
  • Castrate-resistant
  • Clinical trials
  • PET scan
  • Prostate cancer

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Oncology

Cite this

A phase II study of 2-methoxyestradiol (2ME2) NanoCrystal ® dispersion (NCD) in patients with taxane-refractory, metastatic castrate-resistant prostate cancer (CRPC). / Harrison, Michael R.; Hahn, Noah M.; Pili, Roberto; Oh, William K.; Hammers, Hans; Sweeney, Christopher; Kim, KyungMann; Perlman, Scott; Arnott, Jamie; Sidor, Carolyn; Wilding, George; Liu, Glenn.

In: Investigational New Drugs, Vol. 29, No. 6, 12.2011, p. 1465-1474.

Research output: Contribution to journalArticle

Harrison, Michael R. ; Hahn, Noah M. ; Pili, Roberto ; Oh, William K. ; Hammers, Hans ; Sweeney, Christopher ; Kim, KyungMann ; Perlman, Scott ; Arnott, Jamie ; Sidor, Carolyn ; Wilding, George ; Liu, Glenn. / A phase II study of 2-methoxyestradiol (2ME2) NanoCrystal ® dispersion (NCD) in patients with taxane-refractory, metastatic castrate-resistant prostate cancer (CRPC). In: Investigational New Drugs. 2011 ; Vol. 29, No. 6. pp. 1465-1474.
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abstract = "Purpose: 2ME2 (Panzem {\circledR}) 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-PETscans 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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AU - Hahn, Noah M.

AU - Pili, Roberto

AU - Oh, William K.

AU - Hammers, Hans

AU - Sweeney, Christopher

AU - Kim, KyungMann

AU - Perlman, Scott

AU - Arnott, Jamie

AU - Sidor, Carolyn

AU - Wilding, George

AU - Liu, Glenn

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AB - 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-PETscans 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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