Testosterone shows benefit against advanced PCa

An advanced prostate cancer treatment protocol incorporating testosterone shows promise for treating the disease and reversing resistance to androgen deprivation therapy.

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In a small study, published online in Science Translational Medicine (Jan. 7, 2015), researchers tested an approach based on the idea that if prostate cancer cells were flooded with testosterone, the cells might be killed by the hormone shock. The cells also might react by making fewer receptors, which may make the prostate tumor cells vulnerable once more to ADT.

For the study, Samuel Denmeade, MD, and colleagues at Johns Hopkins University, Baltimore, enrolled 16 men who had been receiving testosterone-lowering treatment for metastatic prostate cancer at Johns Hopkins. All had been treated previously with at least one type of ADT and had rising levels of PSA and radiographic evidence their cancers were becoming resistant.

The men were given three 28-day cycles of an intramuscular injection of testosterone and 2 weeks of etoposide (Etopophos). Men who showed decreases in PSA levels after three cycles were continued on testosterone injections alone.

Of the 16 patients, two did not complete the study. One died of pneumonia and sepsis due to the etoposide, and the other experienced prolonged erection, a side effect of the testosterone.

Of the remaining 14 patients, seven experienced a decline in their PSA levels of between 30% and 99%. The other seven men showed no decrease in PSA.

In addition, four of the seven men who experienced a PSA drop stayed on testosterone therapy for 12 to 24 months with continued low PSA levels. Of 10 men whose metastatic cancers could be measured with imaging scans, five experienced tumor shrinkage by more than half, including one man whose cancer completely disappeared.

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“Surprisingly, we saw PSA reductions in all of 10 men, including four whose PSA didn’t change during the trial, who were given testosterone-blocking drugs after the testosterone treatment,” Dr. Denmeade said in a press release from Johns Hopkins. The authors say these results suggest that testosterone therapy has the potential to reverse the resistance that eventually develops to testosterone-blocking drugs like enzalutamide (XTANDI).

Three of the study participants have died since the study began in 2010; the rest are still alive.

During the cycles of etoposide, many of the men experienced the usual side effects of chemotherapy, including nausea, fatigue, hair loss, swelling, and low blood counts. In men receiving only the testosterone injection, however, side effects were rare and usually low grade.

Dr. Denmeade says that more studies are being planned at Johns Hopkins and other institutions.

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