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Hormone-Resistant Prostate Cancer: New Therapies Needed

Hormone-Resistant Prostate Cancer: New Therapies Needed

We read with interest the article, "Hormone-Refractory Prostate Cancer: Choosing the Appropriate Treatment Option," by Drs. Ross and Kantoff in this issue of ONCOLOGY. Prostate cancer is gaining more public attention, and an increasing number of physicians are involved in its treatment. Thus, an extensive review of the management of hormone-refractory prostate caner is welcome.

Pathophysiology and Prognosis

The article is well structured, starting with the biologic basis for the development of metastatic hormone-resistant prostate cancer as well as its natural history. This natural history varies from individual to individual, which must be taken into account while caring for these patients. As the authors point out, patients with a rising prostate-specific antigen (PSA) level without evidence of bone metastases may develop clinical evidence of metastasis only after many years. It is therefore important to take into account the potential side effects of long-term hormonal manipulations, such as an increased risk of diabetes and cardiac disease, which have been documented in a recent publication.[1]

The so-called Halabi nomogram is a valuable prognostic tool in allowing one to prescribe treatment as early as necessary and as late as possible.[2] Prognostic factors such as performance status, Gleason's sum, lactate dehydrogenase (LDH), PSA, hemoglobin, and alkaline phosphatase, as well as the presence or absence of visceral metastases, are important.

Multiple Treatment Options

As pointed out by Drs. Ross and Kantoff, patients with hormone-refractory prostate cancer have several treatment options, including supportive care, secondary hormonal manipulations, chemotherapy, and clinical trials. The importance of best supportive care cannot be overemphasized: The management of these often frail and elderly patients is time-consuming and requires fine clinical skills. All patients requiring narcotic drugs need aggressive management of side effects, particularly nausea and constipation.[3] Careful introduction of these drugs is mandatory.

We appreciated the discussion about secondary hormonal treatments in the article. The addition of an antiandrogen, rotation between antiandrogens, antiandrogen withdrawal, prednisone or prednisone plus ketoconazole, as well as estrogens, all have potential roles in the treatment of the advanced stages of prostate cancer. As pointed out, none of these treatments has been shown to prolong survival, but there are long-term responders, and some of these men might show a survival benefit despite the lack of overall evidence for improvement in median survival in clinical trials.

The paper mentions a study of high-dose bicalutamide (Casodex) at 150 mg/d in combination with hormonal ablation.[4] However, this trial was rather small, and our group does not recommend the use of high-dose bicalutamide for treatment of advanced prostate cancer outside of a clinical trial, because of its potential side effects and high cost.

The authors indicate that an antiandrogen withdrawal phenomena may manifest after 4 to 6 weeks, depending on the half-life of the antiandrogen. While it is important to inform patients of this potential delay (because anxious patients recheck their PSA frequently), antiandrogen withdrawal is quite uncommon and does not appear to occur in the absence of response to adding the antiandrogen.

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