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


METHODS
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.
Harrison
Michael R
MR
University of Wisconsin Carbone Cancer Center, Madison, WI 53705, USA. mrharris@medicine.wisc.edu
Hahn
Noah M
NM
Pili
Roberto
R
Oh
William K
WK
Hammers
Hans
H
Sweeney
Christopher
C
Kim
Kyungmann
K
Perlman
Scott
S
Arnott
Jamie
J
Sidor
Carolyn
C
Wilding
George
G
Liu
Glenn
G
D000077584:2-Methoxyestradiol; D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008297:Male; D008875:Middle Aged; D053758:Nanoparticles; D009362:Neoplasm Metastasis; D049268:Positron-Emission Tomography / Q000379:methods; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019275:Radiopharmaceuticals; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D004958:Estradiol; D000077584:2-Methoxyestradiol