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 language | English (US) |
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Pages (from-to) | 1465-1474 |
Number of pages | 10 |
Journal | Investigational New Drugs |
Volume | 29 |
Issue number | 6 |
DOIs | |
State | Published - Dec 2011 |
Externally published | Yes |
Keywords
- Antiangiogenesis
- Antiproliferative
- Castrate-resistant
- Clinical trials
- PET scan
- Prostate cancer
ASJC Scopus subject areas
- Oncology
- Pharmacology
- Pharmacology (medical)