Randomized phase II study of docetaxel and prednisone with or without OGX-011 in patients with metastatic castration-resistant prostate cancer.

Abstract

PURPOSE:

To determine the clinical activity of OGX-011, an antisense inhibitor of clusterin, in combination with docetaxel/prednisone in patients with metastatic castration-resistant prostate cancer.

PATIENTS AND METHODS:

Patients were randomly assigned 1:1 to receive docetaxel/prednisone either with (arm A) or without (arm B) OGX-011 640 mg intravenously weekly. The primary end point was the proportion of patients with a prostate-specific antigen (PSA) decline of ≥ 50% from baseline, with the experimental therapy being considered of interest if the proportion of patients with a PSA decline was more than 60%. Secondary end points were objective response rate, progression-free survival (PFS), overall survival (OS), and changes in serum clusterin.

RESULTS:

Eighty-two patients were accrued, 41 to each arm. OGX-011 adverse effects included rigors and fevers. After cycle 1, median serum clusterin decreased by 26% in arm A and increased by 0.9% in arm B (P < .001). PSA declined by ≥ 50% in 58% of patients in arm A and 54% in arm B. Partial response occurred in 19% and 25% of patients in arms A and B, respectively. Median PFS and OS times were 7.3 months (95% CI, 5.3 to 8.8 months) and 23.8 months (95% CI, 16.2 months to not reached), respectively, in arm A and 6.1 months (95% CI, 3.7 to 8.6 months) and 16.9 months (95% CI, 12.8 to 25.8 months), respectively, in arm B. Baseline factors associated with improved OS on exploratory multivariate analysis were an Eastern Cooperative Oncology Group performance status of 0 (hazard ratio [HR], 0.27; 95% CI, 0.14 to 0.51), presence of bone or lymph node metastases only (HR, 0.45; 95% CI, 0.25 to 0.79), and treatment assignment to OGX-011 (HR, 0.50; 95% CI, 0.29 to 0.87).

CONCLUSION:

Treatment with OGX-011 and docetaxel was well tolerated with evidence of biologic effect and was associated with improved survival. Further evaluation is warranted.

• Authors: Kim N Chi, Sebastien J Hotte, Evan Y Yu, Dongsheng Tu, Bernhard J Eigl, Ian Tannock, Fred Saad, Scott North, Jean Powers, Martin E Gleave, Elizabeth A Eisenhauer
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 28 Issue 27 Pg. 4247-54 (Sep 20 2010) ISSN: 1527-7755 [Electronic] United States
• PMID: 20733135 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• CLU protein, human
• Clusterin
• OGX-011
• Taxoids
• Thionucleotides
• Docetaxel
• Prostate-Specific Antigen
• Prednisone

Topics

• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Canada
• Clusterin (blood, genetics)
• Disease-Free Survival
• Docetaxel
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Orchiectomy
• Prednisone (administration & dosage)
• Proportional Hazards Models
• Prostate-Specific Antigen (blood)
• Prostatic Neoplasms (blood, drug therapy, secondary, surgery)
• Risk Assessment
• Risk Factors
• Taxoids (administration & dosage)
• Thionucleotides (administration & dosage)
• Time Factors
• Treatment Failure
• Washington