Clinical benefit of atrasentan for men with metastatic hormone-refractory prostate cancer metastatic to bone

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4630-4630 ◽  
Author(s):  
D. J. Sleep ◽  
J. B. Nelson ◽  
D. P. Petrylak ◽  
J. D. Isaacson ◽  
M. A. Carducci
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Disease Progression ◽  
Proportional Hazards ◽  
Cord Compression ◽  
Cox Proportional Hazards ◽  
Hormone Refractory Prostate Cancer ◽  
Double Blind ◽  
The Difference ◽  
Hormone Refractory

4630 Background: Hormone-refractory prostate cancer (HRPC) metastasizes most commonly to bone. Treatment of advanced HRPC patients focuses on alleviating bone pain that afflicts 85% of patients. New therapies are needed that not only prolong survival but slow the progression of morbidity. Atrasentan, a selective endothelin A receptor antagonist that blocks the effect of endothelin in the bone microenvironment by slowing osteoblast proliferation, may slow disease progression in HRPC patients with bone metastases. Methods: Patients enrolled in a randomized, double-blind, placebo-controlled multinational trial of atrasentan 10 mg with independently confirmed bone metastases (N = 690) were followed until the first event of disease progression, which could be by radiographic (≥2 new lesions on bone scan) or clinical means (eg, pain requiring significant opioids or other interventions, spinal cord compression). Analyses were performed on time to disease progression and separately on time to clinical and radiographic progression. The difference between treatments was analyzed using Kaplan-Meier methods and Cox proportional hazards modeling. Results: N = 335 for placebo; N = 355 for atrasentan. Atrasentan therapy resulted in fewer disease progression events relative to placebo and reduced the risk of disease progression by 19% ( Table ). The differential effect of atrasentan on disease progression was most notable against clinical progression (32% reduction in risk vs placebo). Conclusions: In men with HRPC metastatic to bone, atrasentan delays disease progression, especially clinical events, relative to placebo. [Table: see text] [Table: see text]

Evaluation of prostate-specific antigen as a surrogate marker for response of hormone-refractory prostate cancer to suramin therapy.

1995 ◽  
Vol 13 (12) ◽  
pp. 2944-2953 ◽  
Author(s):  
R Sridhara ◽  
M A Eisenberger ◽  
V J Sinibaldi ◽  
L M Reyno ◽  
M J Egorin
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Specific Antigen ◽  
Cox Proportional Hazards ◽  
Hemoglobin Level ◽  
Cox Proportional Hazards Model ◽  
Hormone Refractory Prostate Cancer ◽  
Threshold Values ◽  
Hazards Model ◽  
Hormone Refractory

PURPOSE We evaluated the surrogate role of serum prostate-specific antigen (PSA) using prospectively collected information from patients with hormone-refractory prostate cancer (HRPC) treated with suramin. MATERIALS AND METHODS Data from 103 patients were analyzed using survival analysis, exploratory analysis, and regression analysis. RESULTS There was a significant survival difference between groups of patients with a PSA decrease of < or = 0% or greater than 0% (P = .018). There were no significant overall survival differences between groups of patients with PSA decreases less than 50% or > or = 50% and less than 75% or > or = 75%. Tree-based modeling did not define a specific threshold percentage PSA change as a response criterion. For a response of 1-year survival, sensitivity increased (0.91 v 0.69), but specificity decreased (0.37 v 0.62), with a 75% versus 50% PSA decrease used as classification criterion. Differences between the area under the receiver-operating curves (ROCs) with 50% and 75% PSA decreases as threshold values were small. For a response of 1-year survival, attributable proportions were 0.38 and 0.68, respectively, with 50% and 75% PSA decreases as threshold values. When pretreatment variables were assessed by Cox proportional hazards model, hemoglobin level was the most significant predictor of survival. When percentage PSA change was included in the model, hemoglobin level remained the most significant factor, but percentage PSA change was also a weak, but statistically significant, factor. PSA was a weak, but statistically significant, predictor of survival in Cox proportional hazards model with PSA as a time-variant covariate. CONCLUSION Reduction in PSA level has weak prognostic significance with respect to survival in HRPC patients, but, currently, PSA reduction cannot be used as a reliable response criterion to evaluate treatment efficacy in individual patients. Prospective, randomized studies, including prospective measurement of other indices related to symptomatic clinical benefits, are required.

Hydrocortisone With or Without Mitoxantrone in Men With Hormone-Refractory Prostate Cancer: Results of the Cancer and Leukemia Group B 9182 Study

1999 ◽  
Vol 17 (8) ◽  
pp. 2506-2506 ◽  
Author(s):  
Philip W. Kantoff ◽  
Susan Halabi ◽  
Mark Conaway ◽  
Joel Picus ◽  
Jeffrey Kirshner ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Treatment Failure ◽  
Disease Progression ◽  
Pain Control ◽  
New Drugs ◽  
Survival Duration ◽  
Hormone Refractory Prostate Cancer ◽  
Time To Treatment ◽  
Time To Treatment Failure ◽  
Hormone Refractory

PURPOSE: Approximately 40,000 men die each year of hormone-refractory prostate cancer (HRPC). The results of treatment with chemotherapy have been disappointing to date, with no trials demonstrating a benefit with respect to survival duration. Corticosteroids and mitoxantrone each have been shown to be active agents in this disease. The purpose of this study was to demonstrate an advantage of mitoxantrone and hydrocortisone (M+H) over hydrocortisone alone with respect to survival duration. PATIENTS AND METHODS: Two hundred forty-two patients with HRPC were randomized to receive either M+H or hydrocortisone alone. Patients were monitored for survival, time to disease progression, time to treatment failure, response, and quality-of-life (QOL) parameters. RESULTS: Treatment in both arms was well tolerated. Although there was a delay in time to treatment failure and disease progression in favor of M+H over hydrocortisone alone, there was no difference in overall survival (12.3 months for M+H v 12.6 months for hydrocortisone alone). There was an indication that QOL was better with M+H, in particular with respect to pain control. CONCLUSION: M+H generated more frequent responses and a delay in both time to treatment failure and disease progression compared with hydrocortisone alone. In addition, there was a possible benefit of M+H with respect to pain control over hydrocortisone alone. No improvement in survival was observed. Although M+H could be viewed as a palliative option for patients with HRPC, new drugs and novel strategies are needed to improve survival for this disease.

The risk of renal impairment in hormone-refractory prostate cancer patients with bone metastases treated with zoledronic acid

Cancer ◽  
2007 ◽  
Vol 109 (6) ◽  
pp. 1090-1096 ◽  
Author(s):  
William K. Oh ◽  
Kevin Proctor ◽  
Mari Nakabayashi ◽  
Carolyn Evan ◽  
Lauren K. Tormey ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Zoledronic Acid ◽  
Renal Impairment ◽  
Bone Metastases ◽  
Cancer Patients ◽  
Hormone Refractory Prostate Cancer ◽  
Hormone Refractory

MER-101–03, a multicenter, phase II study to compare MER-101 20mg tablets to intravenous zoledronic acid 4mg in prostate cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5161-5161
Author(s):  
C. McHugh ◽  
K. Madigan ◽  
A. Walsh ◽  
J. Fox ◽  
T. W. Leonard ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Zoledronic Acid ◽  
Bone Metastases ◽  
Cancer Patients ◽  
Phase Ii ◽  
Performance Status ◽  
Hormone Refractory Prostate Cancer ◽  
Open Label ◽  
Secondary Endpoints ◽  
Hormone Refractory

5161 Background: The primary objective of this study is to examine the pharmacodynamic effects of two different regimens of zoledronic acid, Orazol 20 mg tablets versus Zometa 4mg IV infusion once-monthly therapy on biomarkers in male bisphosphonate-naïve hormone-refractory prostate cancer patients. Methods: The study is an open-label, multi-center phase II clinical trial to compare oral Orazol 20 mg tablets weekly, to infusions of intravenous Zometa 4mg monthly, in males with hormone-refractory prostate cancer, bone metastases, and no prior bisphosphonate treatment. Patients were assigned into one of three cohorts. The three treatments administered were IV Zometa, 4 mg, 15 minute infusion, Day 0 and Day 28; Orazol po, 20 mg, Days 0, 7, 14, 21, 28, 35, 42, and 49; and Orazol po, 20 mg, Days 0, 1, 2, 3, 28, 35, 42, and 49. The study population consisted of men with hormone refractory prostate cancer as evidenced by history of rising PSA levels (last 2 of 3 PSA levels must be above nadir), who are bisphosphonate-naive, and have radiographically-confirmed bone metastases. Efficacy assessments: The primary endpoints are the assessment of response of four biomarkers, urinary NTX, serum CTX, serum bone specific alkaline phosphatase, and serum calcium on days -7, 0, 7, 14, 21, 28, 35, 42, 49, and 56. Secondary endpoints are assessments of performance and pain scores based on ECOG performance status, BPI, and analgesic use. Safety assessments include physical examinations, vital signs and body weight, hematology panel, urinalysis, and blood chemistry panel. Results: The results demonstrated a rapid decrease for all four biomarkers. This decrease was seen at seven days, and was sustained throughout the study. There were no statistically significant differences between any of the treatments in the primary and secondary endpoints. Conclusions: From the results of MER-101–03, Orazol weekly therapy appears to be as effective as Zometa, based on the biomarkers analyzed. Orazol offers a substantial improvement in therapy over IV infusion for patients, with efficacy that is at least comparable based on the results obtained here. No significant financial relationships to disclose.

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