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Case History

Image not available. A 72-year-old man with known prostate cancer is followed up regularly in clinic. He was diagnosed as having locally advanced cancer and was started on goserelin 23 months ago. His prostate-specific antigen (PSA) level has continued to rise over the past 6 months despite the addition of bicalutamide. He feels very well and has no comorbidities.

What other hormone treatments can be used?

Is chemotherapy an option?

What other options are available for him?

Background

Image not available. Hormone ablation treatment with luteinizing hormone releasing hormone (LHRH) agonists alone or in combination with complete androgen blockade (CAB) has become the mainstay of treatment for patients with advanced/metastatic prostate cancer. The definition of hormone-refractory prostate cancer (androgen-independent, androgen-refractory, or hormone-independent) in a man who has undergone androgen deprivation treatment (ADT) requires the demonstration of functionally castrate levels of serum testosterone (Image not available.1.7 nmol/l [50 ng/dl]) with biochemical and/or clinical evidence of disease progression. The options for systemic treatment in such men include second-line hormone treatment, systemic chemotherapy and adjunctive treatment including experimental therapies. However, there is no standard approach.

Discussion

What other hormone treatments can be used?

Image not available.

  • Second-line hormone treatment options are withdrawal of anti-androgens

  • administration of other anti-androgens (non-steroidal anti-androgens such as flutamide, bicalutamide and nilutamide; steroidal antiandrogens such as cyproterone acetate and megestrol)

  • other hormones including oestrogen (diethylstilbestrol and glucocorticoids, e.g. dexamethasone or prednisone).

The overall response rates vary from 20% to 60% depending on when used but tend to be short lived.

Current guidelines recommend that the first approach should be:1

  • discontinuation of anti-androgens if the patient is receiving CAB

or

  • addition of an anti-androgen if LHRH agonist monotherapy is being administered.

The 'anti-androgen withdrawal syndrome' occurs in approximately 20% of men in whom CAB is unsuccessful and some experience symptomatic or objective improvement. Diethylstilbestrol is a non-steroidal oestrogen and clinical trials showed that it is as effective as orchidectomy in treating metastatic prostate cancer. However, there are more cardiovascular and thromboembolic complications.2 A dose of 1 mg/day appears to be as effective as 5 mg/day, but it does not lower serum testosterone to castrate levels in all men. The testosterone level frequently begins to rise after 6 to 12 months of treatment.3 Continuation of primary testicular androgen deprivation is recommended. The median survival of men with hormone-refractory prostate cancer is approximately 12 months.4

Is chemotherapy an option?

Chemotherapy was previously considered to be relatively ineffective in hormone-refractory prostate cancer.5 In early trials, objective response rates were 8.7%,6 and median survival did not exceed 12 months. Estramustine phosphate (EMP) alone or in combination with taxanes or vinca alkaloids showed PSA response rates in 25–86% of patients.

Regimens ...

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