Originally published as JCO Early Release 10.1200/JCO.2007.15.9830 on November 24 2008

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Phase III Trial of Androgen Ablation With or Without Three Cycles of Systemic Chemotherapy for Advanced Prostate Cancer

Randall E. Millikan, Sijin Wen, Lance C. Pagliaro, Melissa A. Brown, Brenda Moomey, Kim-Anh Do, Christopher J. Logothetis

From the Departments of Genitourinary Medical Oncology and Biostatistics, University of Texas M.D. Anderson Cancer Center, Houston, TX

Corresponding author: Randall Millikan, PhD, MD, Department of Genitourinary Medical Oncology, University of Texas M.D. Anderson Cancer Center, 1155 Pressler, CPB7.3462, Houston, TX 77030; e-mail: rmillika{at}mdanderson.org

Purpose We conducted a phase III trial in patients with previously untreated metastatic prostate cancer to test the hypothesis that three 8-week cycles of ketoconazole and doxorubicin alternating with vinblastine and estramustine, given in addition to standard androgen deprivation, would delay the appearance of castrate-resistant disease.

Patients and Methods Eligible patients had metastatic prostate cancer threatening enough to justify sustained androgen ablation and were fit enough for chemotherapy. The primary end point was time to castrate-resistant progression as shown by increasing prostate-specific antigen, new radiographic lesions, worsening cancer-related symptoms, or receipt of any other systemic therapy.

Results Three hundred six patients were registered; 286 are reported. Median time to progression was 24 months (95% CI, 18 to 39 months) in the standard therapy arm, and 35 months (95% CI, 26 to 44 months) in the chemohormonal group (P = .39). At median follow-up of 6.4 years, overall survival was 5.4 years (95% CI, 4.7 to 7.8 years) in the standard therapy arm versus 6.1 years (95% CI, 5.1 to 10.1 years; P = .41). Prostate-specific antigen kinetics at the time of androgen ablation and the nadir after hormone treatment were strongly correlated with survival. Chemotherapy significantly increased the burden of therapy, with 51% of patients experiencing an adverse event of grade 3 or worse, especially thromboembolic events.

Conclusion There is no role for ketoconazole and doxorubicin alternating with vinblastine and estramustine before emergence of a castrate-resistant phenotype.

published online ahead of print at www.jco.org on November 24, 2008.

Presented in part at the Annual Meeting of the American Urologic Association May 8-13, 2004, San Francisco, CA.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical trial information can be found for the following: NCT00002855 [ClinicalTrials.gov] .

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