Prostate Cancer Expert Forum
Therapy strategy
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Therapy strategy

Dear Dr. Tewari,

My brother-in-law is a South Indian, 50 of age who weighs 71.0 Kg. He is generally in excellent health, married, with two children. He was diagnosed with metastatic prostate cancer in August 2007. Needle biopsy was used to estimate grade III Gleason score of 6. His initial PSA was (>50.0 ng/mL) on August 21, 2007. He underwent a bilateral orchiectomy and was treated with bicalutamide and zoledronic acid. He has bone metastases in spine and hip with some pain. His PSA has been climbing: March 19, 2008 (0.17 ng/mL) PSA. June 12, 2008 (7.24 ng/mL) PSA. July 22, 2008 (28.32 ng/mL). The PSA velocity seem extremely high. The dose of bicalutamide has now been increased to reduce the PSA and he is still taking zoledronic acid. My question: At what point (PSA) should he be prescribed ketoconazole or taxotere + prednisone? The cancer cells are likely producing androgen within the tumor? Will ketoconazole be beneficial? When should he consider clinical trials such as GVAX or abiraterone as some trials require that the patient not received more than one series of taxotere. Any recommendations for a second opinion in India?

A million thanks.

Brad  

Tags: prostate
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242579_tn?1252114771
Hello Brad,
It seems as though your brother-in-law has symptomatic metastases with, indeed, a high PSA velocity, in spite of treatment with the anti-androgen bicalutamide.  There may be a possibility that his cancer has acquired androgen resistance, which means that even increasing the bicalutamide may not lower his PSA or provide symptomatic relief. The administration of ketoconazole or glucocorticoids (prednisone), which can suppress may result in both objective disease response and symptomatic benefit, even in men who are refractory to androgen deprivation therapy.  Ketoconazole has been known to decrease PSA levels dramatically and in a relatively short time period.  There is no set PSA value to begin taxotere/prednisone therapy.  Instead, PSA doubling time (the time is takes for the PSA to double) and PSA velocity are considered, which are high with your brother-in-law.  Taxotere/prednisone is an approved chemotherapy regimen for men with hormone refractory prostate cancer in the US.  GVAX is being studied as treatment for hormone refractory prostate cancer, however taxotere/prednisone is currently the standard. Abiraterone is a drug that is taken orally and inhibits an enzyme called CYP450c17, which is critical to the production of the male hormones , not only in the testes, but also at other sources. In several trials, the drug has produced PSA decline rates by greater than 50% in 60% of pre-taxotere patients and 50% of post-taxotere patients. These results are supported by evidence of tumor shrinkage on scans, drops in circulating tumor cell counts and improvements in symptoms.
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