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Second-line hormonal therapies

Initial hormone ablation controls symptoms for 18 months to two years in the average patient. In the past, patients typically presented with new urinary symptoms or new bone pain while receiving castration treatment but with the advent of PSA determinations, most of these patients can be identified by a rising PSA prior to symptom onset. It is unclear whether these patients should be treated immediately or whether therapy should be delayed until the onset of symptoms.

Several strategies have been employed as secondary hormonal treatments. In general, responses are seen in about 20% of patients and usually last approximately six months.

In this Section:

• Addition or subtraction of flutamide
• Aminoglutethimide (Cytadren) and hydrocortisone
• Ketaconazole

 

Addition or subtraction of flutamide

If a patient has been receiving monotherapy, flutamide is typically added, but responses are seen in only about 10% of patients. In patients who have been treated with CAB, omitting flutamide from the regimen can cause a paradoxical shrinkage of measurable disease, a decrease in serum PSA, and/or a lessening of symptoms in 10%-25% of patients. Thus, the addition or subtraction of flutamide has become the next step for patients in whom initial hormone therapy is ineffective. If this measure fails, another second-line agent is often employed.

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Aminoglutethimide (Cytadren) and hydrocortisone

Aminoglutethimide (Cytadren) and hydrocortisone have been widely used. Aminoglutethimide is started at a dose of 125 mg PO qid and increased to 250 mg PO qid. It is associated with significant side effects, including lethargy, weakness, rash, and fever.

Hydrocortisone (20 mg PO bid) alone affords significant pain relief, as well as occasional objective tumor responses.

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Ketaconazole

Ketaconazole, with or without hydrocortisone, is also used. Ketoconazole is started at a dose of 200 mg PO tid and then escalated to a total dose of 400 mg tid. The 1,200mg daily dose is associated with nausea and vomiting, however, and can result in severe liver injury. Patients receiving high-dose ketoconazole need to be monitored carefully for signs and symptoms of liver damage, and the drug should be stopped immediately if liver enzymes become elevated.

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