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In men with nonmetastatic prostate cancer treated with intermittent androgen deprivation, thalidomide (Thalomid) significantly prolonged progression-free survival compared with placebo.
Bethesda, MD-In men with nonmetastatic prostate cancer treated with intermittent androgen deprivation, thalidomide (Thalomid) significantly prolonged progression-free survival (PFS) compared with placebo, according to data from a National Cancer Institute-sponsored clinical trial.
Patients treated with thalidomide following two courses of androgen deprivation had a median PFS of 17.1 months versus 6.6 months for men treated with placebo. Thalidomide resulted in a nonsignificant improvement in PFS following an initial course of androgen deprivation therapy, first author William D. Figg, PharmD, reported at the American Society of Clinical Oncology annual meeting in Chicago.
"Clinically, thalidomide has activity in androgen-independent prostate cancer," said Dr. Figg, head of molecular pharmacology in the Medical Oncology Branch at NCI. "Thalidomide prolonged progression-free survival following intermittent androgen ablation in patients with D0 prostate cancer, but it did not alter recovery of testosterone or dihydrotestosterone after androgen deprivation."
Dr. Figg reported findings from a multicenter clinical trial involving 159 patients who had had PSA recurrence following definitive treatment of prostate cancer with surgery or radiation therapy. All patients received leuprolide for 6 months and then were randomized to thalidomide or placebo, which was continued until a patient's PSA level returned to the baseline level or increased to ≥5 ng/mL.
Following the PSA rise during treatment with thalidomide or placebo, pa-tients received an additional 6 months of leuprolide, and then were re-randomized to thalidomide or placebo, which was continued until PSA rise. Patients who developed metastatic disease were immediately withdrawn from the study.
The primary outcome measure was PFS. Secondary objectives included safety and toxicity, pharmacokinetic characterization, and analysis of testosterone and dihydrotestosterone (DHT).
The patients' median age was 68 years, and they had median Gleason scores and on-study PSA levels of 7 and 5.1 ng/mL, respectively. Most had Eastern Cooperative Oncology Group performance status of 0, and median baseline testosterone values were 311.5 ng/mL prior to the first course of androgen deprivation and 326 ng/mL prior to the second course.
The median times to normalization of testosterone and DHT after the first course of androgen deprivation were 15.4 weeks and 15.2 weeks, respectively, and did not differ between the thalidomide and placebo groups. Following the second course of androgen deprivation, the median time to normalization was 18 to 19 weeks for testosterone and DHT and did not differ between treatment groups.
The median time to progression after the first course of androgen deprivation was 15 months with thalidomide and 6.6 months with placebo (p=.21). Following the second course of androgen deprivation, patients randomized to thalidomide had almost a threefold increase in median PFS with thalidomide (17.1 vs. 6.6 months, p=.0002).
Regarding the lack of difference in PFS following initial androgen deprivation, Dr. Figg said the finding might reflect the natural history of hormone-sensitive disease, the possibility that a majority of patients would respond well to androgen deprivation regardless of additional treatment, or the possibility that thalidomide's benefits might not be readily apparent in that clinical setting.
The most likely explanation, however, is that the sample size was too small to detect a difference, he added.
Grade 3 or 4 toxicity was infrequent but occurred more often during treatment with thalidomide. The most common adverse effects were fatigue, dizziness, and sexual dysfunction, which occurred in six, five, and five patients, respectively, treated with thalidomide.