Much research had gone on about the effects of thalidomide and the related drug Revlimid on prostate cancer. At the International Conference on Molecular Targets and Cancer Therapeutics in November of 2005, held in Philadelphia, Pennsylvania, an abstract was presented by Dr. Robert J. Amato. This conference was organized jointly by the American Association for Cancer Research, the National Cancer Institute, and the European Organization for Research and Treatment of Cancer. In Dr. Amato’s paper, eighteen prostate cancer patients were treated with Leukine and thalidomide. All had rising PSAs following local therapy, and had not previously been treated with hormone blockade. All of the men in his study had at least a 26% reduction in their level of PSA, with a median reduction of 59%. His response rate was 100%. Since then a variety if combinations of thalidome with drugs such as bevacizumab and docetaxel have been published. Several studies comparing docetaxel alone to docetaxel plus thalidomide have been published. One study showed a 53% response rate for the combination therapy compared to a 37% response rate for docetaxel alone, and median progression free survival for the combination arm was 5.9 months (survival of 25.9 months) compared to progression free survival of 3.7 months (survival 14.7 months) in the docetaxel only arm. Another docetaxel plus thalidomide study showed 18 month survival in 69.3% of patients compared to 47.2% of patients treated with docetaxel alone (P <.05). As a single agent in another study, it produced a decline in serum PSA of at least 50% in three men (15%) showed , sustained throughout treatment. Of 16 men treated for at least 2 months, six (37.5%) showed a fall in absolute PSA by a median of 48%. In a 2003 study, 27% of all patients had a decline in PSA of > or = 40%, often associated with an improvement of clinical symptoms.
All this would be considered preliminary. Fortunately, now a new randomized phase 2 study has recently been published. Thalidomide may have use in the treatment of men who have biochemical recurrence of prostate cancer or a rise in their prostate-specific antigen (PSA) count after definitive therapy, according to this study from the National Cancer Institute. In this population, the use of thalidomide was associated with an increase in PSA progression-free survival after intermittent androgen-deprivation therapy (ADT). The median time to a new PSA increase was 17.1 months for thalidomide (vs 6.6 months for placebo) in the second phase of the study’s crossover design. Thalidomide is listed by AHFS and in Micromedex. All patients in the study had androgen-dependent adenocarcinoma of the prostate and 2 consecutively increasing PSA counts after local definitive therapy with radical prostatectomy, radiation therapy, or cryosurgery.
In phase A of the analysis, 147 patients were initially administered gonadotropin-releasing hormone agonists (GnRH-A) for 6 months, and subsequently received thalidomide or placebo. GnRH-A generally consisted of leuprolide (22.5 mg for 3 months) or goserelin (10.8 mg for 3 months).
For patients in phase A, the median time to PSA progression for those taking thalidomide was 15 months, compared with 9.6 months for those taking placebo (P = .21). Once patients had PSA progression, defined by an increasing PSA greater than 5 ng/mL or reaching a minimum of 1 ng/mL, they were retreated with a GnRH-A for another 6 months, and then crossed over to the opposite treatment. This was phase B, which was completed by 88 patients. The median time to PSA progression during phase B for the thalidomide group was 17.1 months, and for the placebo group was 6.6 months (P = .0002).
Revlimid is closely related to Thalidomide, but is better tolerated and a number of studies have suggested that it is of benefit in hormone resistant population.
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