IngentaConnect The VIOXX in prostate cancer prevention study: cardiovascular eve...

Authors: van Adelsberg, Janet¹; Gann, Peter²; Ko, Amy T.¹; Damber, Jan-Erik³; Logothetis, Christopher⁴; Marberger, Michael⁵; Schmitz-Drager, Bernd J.⁶; Tubaro, Andrea⁷; Roehrborn, Celiaus⁸

Source: Current Medical Research and Opinion, Volume 23, Number 9, September 2007 , pp. 2063-2070(8)

Publisher: Informa Healthcare

Abstract:

Background: A double-blind, randomized, placebo-controlled study was designed to determine the cumulative incidence of developing prostate cancer over 6 years of treatment with rofecoxib 25 mg/day versus placebo. Before completion, this trial was terminated following the voluntary withdrawal of rofecoxib. (On September 30, 2004, Merck & Co., Inc. announced the voluntary worldwide withdrawal of rofecoxib from the market.) Here we report the cardiovascular (CV) safety data collected from this study.

Methods: A total of 4741 men (44-81 years old) exhibiting prostate-specific antigen levels (PSA) between 2.5 and 10 ng/mL were enrolled. Patients were stratified by PSA level and use of low-dose aspirin (LDA), then randomized to rofecoxib 25 mg (n = 2369) or placebo (n = 2372). Safety data were analyzed in all patients receiving ≥1 dose of study medication. All reported thrombotic CV events occurring on-treatment or within 14 days after study drug discontinuation were adjudicated by an independent panel of clinical experts blinded to treatment assignment. Rates per 100 patient-years and relative risk (RR) of thrombotic CV events, rofecoxib vs. placebo, were determined.

Results: Approximately 36% of patients had ≥2 CV risk factors or LDA indicated. Median treatment duration was 4.14 (range: 0.03-15.90) months. Twenty-nine patients (14 rofecoxib, rate 1.27; 15 placebo, rate 1.36) experienced confirmed thrombotic CV events; RR 0.94 (95% CI: 0.45, 1.94) vs. placebo. Four patients (one rofecoxib; three placebo) died due to a confirmed thrombotic event. Significantly (p = 0.002) more patients receiving rofecoxib (n = 20; 0.8%) experienced hypertension-related adverse events versus placebo (n = 2; 0.1%). There were no cases of congestive heart failure.

Conclusions: Rofecoxib 25 mg and placebo demonstrated similar risk of thrombotic CV events in this limited dataset.

Keywords: CARDIOVASCULAR; PROSTATE CANCER; ROFECOXIB; SAFETY

Document Type: Research article

DOI: 10.1185/030079907X219526

Affiliations: 1: Merck Research Laboratories, Rahway, NJ, USA 2: Department of Pathology, University of Chicago, Chicago, IL, USA 3: Department of Urology, Sahlgrenska University, Gothenburg, Sweden 4: Genitourinary Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA 5: Department of Urology, University of Vienna, Austria 6: Department of Urology, Euromed Clinic, Fürth, Germany 7: Department of Urology, La Sapienza University, Rome, Italy 8: Department of Urology, University of Texas, Dallas, TX, USA

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The VIOXX in prostate cancer prevention study: cardiovascular events observed in the rofecoxib 25 mg and placebo treatment groups