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.
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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)
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Chemical References |
- Antineoplastic Agents
- Radiopharmaceuticals
- Fluorodeoxyglucose F18
- Estradiol
- 2-Methoxyestradiol
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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
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