Even among patients with metastatic hormone-refractory prostate cancer, some heterogeneity is found in prognosis and in retained hormone sensitivity. In such patients who have symptomatic bone disease, several factors are associated with worsened prognosis: poor performance status, elevated alkaline phosphatase, abnormal serum creatinine, and short (<1 year) previous response to hormone therapy. The absolute level of PSA at the initiation of therapy in relapsed or hormone-refractory patients has not been shown to be of prognostic significance. Some patients whose disease has progressed on combined androgen blockade can respond to a variety of second-line hormonal therapies. Aminoglutethimide, hydrocortisone, flutamide withdrawal, progesterone, ketoconazole, and combinations of these therapies have produced PSA responses in 14% to 60% of patients treated and have also produced clinical responses of 0% to 25% when assessed. The duration of these PSA responses has been in the range of 2 to 4 months. Survival rates are similar whether ketoconazole plus hydrocortisone is initiated at the same time as anti-androgen (e.g., flutamide, bicalutamide, or nilutamide) withdrawal or when PSA has risen after an initial trial of anti-androgen withdrawal as seen in the CLB-9583 trial, for example.[Level of evidence: 1iiA] Data on whether PSA changes while on chemotherapy are predictive of survival are conflicting.[33,36]
Patients treated with either luteinizing-hormone agonists or estrogens as primary therapy are generally maintained with castrate levels of testosterone. One study from the Eastern Cooperative Oncology Group showed that a superior survival resulted when patients were maintained on primary androgen deprivation; however, another study from the Southwest Oncology Group did not show an advantage to continued androgen blockade.
Low-dose prednisone may palliate symptoms in some patients. In a randomized comparison of prednisone (5 mg 4 times per day) with flutamide (250 mg 3 times per day) in patients with disease progression after androgen-ablative therapy (castration or luteinizing hormone-releasing hormone [LHRH] agonist), prednisone and flutamide produced similar survival, symptomatic response, PSA response, and time to progression; however, there were statistically significant differences in pain, nausea and vomiting, and diarrhea in patients who received prednisone. (Refer to the Pain and the Nausea and Vomiting summaries; for information on diarrhea, refer to the Gastrointestinal Complications summary.) Ongoing clinical trials continue to explore the value of chemotherapy for these patients.[18,24,25,26,41,42,43,44]
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent prostate cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
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