Prostate Cancer- ABLIN FOUNDATION

Androgen Dependence and Independence

Prostate cancer cells generally require hormone, or androgen, as 'food' for growth. Androgen dependence is the term used to describe this phenomenon; the cancer cells are dependent upon the hormones (such as testosterone, an androgen) for growth. The rationale for the use of androgen blockade (Lupron, Casodex, Zoladex, etc.) is that by reducing the testosterone available as 'food' for the cancer cells, the cancer will die.

Unfortunately, not all cancer cells are hormone-dependent, and some hormone-dependent cells may become hormone-independent, somewhat analgous to bacteria becoming resistant to antibacterial drugs. Hormone-independent cancer cells do not 'feed' upon testosterone for growth and therefore androgen blockade therapy does not kill these cancer cells. Patients with hormone-independent cancers are also called 'hormone refractory'.

(Note: Earlier studies by Ablin et al., e.g., in Cancer Res., 38:3702, 1978 and Amer. J. Reprod. Immunol., 1:206, 1981, among other reports from this group, demonstrated stilbestrol to have an immunosuppressive effect in patients with prostate cancer and would be contraindicated in any patients who might be candidates for immunotherapy.)

Stilbestrol Effective As Salvage Therapy For Refractory Prostate Cancer

WESTPORT, Jul 07 (Reuters Health) - Low-dose stilbestrol, in combination with hydrocortisone, reduces symptoms and lowers prostate-specific antigen (PSA) levels in patients with refractory prostate cancer, according to a report in the June issue of the British Journal of Urology International.

Higher doses of stilbestrol (3 mg/day to 5 mg/day) have proven efficacious in metastatic prostate cancer, but in at least one study, gains in survival were offset by excess cardiovascular deaths resulting from its thromboembolic properties, the authors explain.

Dr. R.T.D. Oliver, of St. Bartholomew's Hospital, in London, UK, and colleagues investigated the effectiveness of low-dose (1 mg/day) stilbestrol (SB) in 34 men with metastatic prostate cancer refractory to androgen suppression. "In an attempt to reduce the incidence of thromboembolic events, aspirin (75 mg/day) was also added."

Among 29 patients whose symptoms could be evaluated, 25 reported an improvement and four reported no change or a worsening of symptoms, the authors report. The symptom response persisted a median 6 months.

Median PSA levels improved from 292 ng/mL to a nadir of 66 ng/mL, a median decrease of 84%. The PSA nadir occurred a median 4 months into treatment, and the PSA response persisted a median 6 months.

Seven of eight patients with a PSA decrease of greater than 90% reported improved symptoms, the investigators note, compared with 17 of 19 patients experiencing a lower PSA reduction. Also, the subgroup of men with the greatest PSA reduction showed a trend for longer progression-free survival.

Adverse events included fluid retention and edema in 11 men, three cases of heart failure, and two episodes of deep vein thrombosis, the report indicates.

"This phase II study showed that the combination of SB and hydrocortisone was highly effective and had an acceptable side-effect profile as a salvage regimen, although probably not as first-line therapy," the authors conclude. "However, it may yet be possible to adapt such an inexpensive and effective regimen for use at an earlier stage in advanced prostate cancer."

Br J Urol Int 2000;85:1069-1073.

These observations, albeit limited to 34 patients, are similar, including the side effects, e.g., thrombosis, to those reported for PC-SPES, but at a substantially lower cost.

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