A Double-Blind Randomized Crossover Study of Oral Thalidomide Versus Placebo for Androgen Dependent Prostate Cancer Treated With Intermittent Androgen Ablation

Received 26 August 2008 published online 23 January 2009.

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Purpose

We determined whether thalidomide can prolong progression-free survival in men with biochemically recurrent prostate cancer treated with limited androgen deprivation therapy.

Materials and Methods

A total of 159 patients were enrolled in a double-blind randomized trial to determine if thalidomide can improve the efficacy of a gonadotropin-releasing hormone agonist in hormone responsive patients with an increasing prostate specific antigen after primary definitive therapy for prostate cancer. Patients were randomized to 6 months of gonadotropin-releasing hormone agonist followed by 200 mg per day oral thalidomide or placebo (oral phase A). At the time of prostate specific antigen progression gonadotropin-releasing hormone agonist was restarted for 6 additional months. Patients were then crossed over to the opposite drug and were treated until prostate specific antigen progression (oral phase B). Testosterone and dihydroxytestosterone were likewise monitored throughout the study.

Results

During oral phase A the median time to prostate specific antigen progression was 15 months for the thalidomide group compared to 9.6 months on placebo (p = 0.21). The median time to prostate specific antigen progression during oral phase B for the thalidomide group was 17.1 vs 6.6 months on placebo (p = 0.0002). No differences in time to serum testosterone normalization between the thalidomide and placebo arms were documented during oral phase A and oral phase B. Thalidomide was tolerable although dose reductions occurred in 47% (58 of 124) of patients.

Conclusions

Despite thalidomide having no effect on testosterone normalization, there was a clear effect on prostate specific antigen progression during oral phase B. This is the first study to our knowledge to demonstrate the effects of thalidomide using intermittent hormonal therapy.

Key Words: prostatic neoplasms, hormones, thalidomide, disease-free survival, angiogenesis inhibitors

a Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland

b Molecular Pharmacology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland

c Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland

d Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland

e Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, Maryland

f Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland

g Departments of Internal Medicine and Urology, University of Michigan Medical Center, Ann Arbor, and Department of Medical Oncology, Wayne State University/Barbara Ann Karmanos Cancer Institute, Detroit, Michigan

h Department of Medicine, New York-Presbyterian Hospital/Columbia University Medical Center, New York, New York

i Departments of Medicine and Urology, University of Washington, Seattle, Washington

j Department of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania

k Tulane Medical School, New Orleans, Louisiana

Correspondence: Medical Oncology Branch, National Cancer Institute, Bldg 10/Room 5A01, 9000 Rockville Pike, Bethesda, Maryland 20892 (telephone: 301-402-3623; FAX: 301-402-8606)

Supported by the Intramural Research Program of the National Institutes of Health, NCI, Center for Cancer Research.

Study received institutional review board approval.

Clinical Trials identifier NCT00020085 (www.clinicaltrials.gov).

For other articles on related topics see pages 1361, 1372 and 1381.

† Financial interest and/or other relationship with Neogenix Oncology Inc.

PII: S0022-5347(08)03053-X

doi:10.1016/j.juro.2008.11.026

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