The first approved chemotherapy agents used to help control the pain and symptoms associated with the metastasis of prostate cancer were – mitoxantrone (Mitoxantrone) and estramustine (Emcyt). However, due to their severe side-effects, most doctors were reluctant to recommend them as a suitable treatment. Not even when a patient’s cancer was considered to be in a state of progression was it used (even when a patient’s quality of life was considered to be above average [good]).
However, docetaxel (Taxotere) was at the center of two recent phase-3 trial successes, where the FDA (Food and Drug Administration) finally approved its use for the treatment of metastatic prostate cancer.
It should be noted that chemotherapy is only usually given to prostate cancer sufferers after the development of hormone-refractory (androgen-independent) prostate cancer (defined by the growth of cancer [not taking into consideration the castrate testosterone levels]) – raising PSA level, radiographic study changes, and worsening pain symptoms, etc., and when secondary hormonal medicines such as ketoconazole (Nizoral) may be prescribed (prior to chemotherapy treatment).
A recent study was taken where 38 patients with advanced prostate cancer (refractory to at least initial testicular androgen deprivation) were given ketoconazole in high-doses (400 mg 3-times a day), together with physiologic replacement doses of glucocorticoids (hydrocortisone, 20 mg [also 3-times a day]) concluded with the following results: 30 patients were completely evaluable, with 6-patients being withdrawn due to a possible ketoconazole-related toxicity.
Further to these results, 2-patients were considered invaluable due to either inter-current therapy, or the inability to maintain follow-up. In general, ketoconazole was tolerated by most of the 38 patients, with only mild nausea and vomiting occurring (37% of patients), dose modification (3-patients), no hepatic damage (relating to the liver) observed, and with only 5-patients responding well to ketoconazole (determined by palpable or radiographic).
Ketoconazole was originally developed as an anti-fungal antibiotic (a substituted imidazole [a white crystalline basic heterocyclic compound; 1,3-diazole – formula: C 3 H 4 N 2 ]) that is able to inhibit ergosterol synthesis in fungi and cholesterol synthesis in mammalian cells. However, it was quickly noticed that ketoconazole had the ability to suppress both testicular and adrenal steroidogenesis.
However, it should be noted that although ketoconazole (when used with hydrocortisone) has the ability to suppress plasma androgens in advanced prostatic cancer patients, the regression of such cancer can again become prevalent at a later date. Also it should be noted that; although, an advancement – the ketoconazole agent does not at this moment-in-time offer any proven benefits to an advanced prostate cancer patient’s overall survival rate, and where it is expected to be many years before there will be any significant evidence of benefits (if any are to become apparent) to using ketoconazole.