The occasionally discussed, but not often used, alternative hormone therapy, transdermal estrogen might be ready to soon move on to a phase III trial. A poster presentation of a phase II trial showed that transdermal estrogen patches drove down testosterone and PSA levels to a similar extent as an LHRH analog. The poster presentation was offered by Ruth E. Langley, M.D., of the Medical Research Council in London and reported at the Genitourinary Cancers Symposium.

The really big news is that there were no worrisome adverse events experienced with the estrogen patches, as opposed to the myriad of negative side effects we experience with traditional LHRH analog therapies. Additionally, unlike conventional androgen deprivation therapy, the patches could help preserve bone mineral density, another prolem from lowering testosterone levels.

“These data demonstrate that estrogen patches produce a similar fall in testosterone to LHRH analogs and concomitant falls in PSA in patients with metastatic and locally advanced prostate cancer,” said Dr. Langley. “The patches have been generally well tolerated.”

Oral estrogen had been used as a hormonal therapy for prostate cancer in the 1960s. However, it was associated with increased cardiovascular morbidity so most doctors stopped using the estrogen as a therapy.

According to Dr. Langley, “The

[cardiovascular] toxicity has been attributed to first-pass hepatic metabolism, which affects lipids and coagulation proteins,”. Since trancutaneous administration of estrogen avoids the enterohepatic circulation, it should not be associated with the same high levels of cardiovascular toxicity.” The cardiovascular safety data from the trial has not yet been released, pending accrual of the 200-patient total for the study.

Nonetheless, on the basis of the results, the data monitoring committee, recommended that investigators “focus their plans towards developing a larger, phase III trial,” said Dr. Langley.

In a preliminary trial involving 20 patients with prostate cancer, estrogen patches lowered testosterone to castrate levels and caused no cardiovascular events, aside from one case of edema.

On the basis of those results, investigators organized a multicenter, randomized study that included 172 patients as of mid-February, 2009. The trial involved patients with newly diagnosed T3/4 prostate cancer or with cancer in PSA relapse following definitive surgery or radiation therapy. Castrate-level testosterone was defined as <50 ng/dL. The patients were randomized 1:2 to an LHRH analog or to transdermal patches that released 100 µg of estradiol per hour. After a planned review of data, investigators increased the patch dosage. As a result, the first 33 patients randomized to transdermal patches received three patches, which were changed twice weekly. The remaining patients assigned to the estrogen group received four patches that were changed twice weekly. Estradiol, testosterone, and PSA levels were measured at four weeks and three months and then every six months. In addition, investigators measured PSA levels at nine, 15, and 21 months. At week four, 20 of 33 patients (60.6%) in the LHRH analog group had castrate levels of testosterone, as did 20 of 30 (66.6%) who received three estradiol patches, and 30 of 33 (90.9%) who received four patches. Four LHRH analog patients had testosterone levels between 50 and 100 ng/dL, compared with five in the three-patch group and three in the four-patch group. By week 12, 26 of 28 evaluable patients (92.8%) assigned to the LHRH analog had castrate levels of testosterone, and none had levels between 50 and 100 ng/dL. Among patients treated with three estradiol patches, 21 of 29 (72.4%) had castrate levels of testosterone and six had levels of 50 to 100 ng/dL. In the four-patch group, 27 of 31 patients (87%) had castrate testosterone levels and the other four had levels of 50 to 100 ng/dL. At six months, the median testosterone levels were 14.3 ng/dL in the LHRH analog group, 28.6 ng/dL in the three-patch group, and 22.9 ng/dL in the four-patch group. Median PSA values were 0.9 ng/mL, 3.2 ng/mL, and 1.3 ng/mL, respectively. The transdermal patches shows cleaar potential of being very useful as an alternative hormone therapy. Currently estrogen is not approved as a therapy for prostate cancer and the information in this post has not yet appeared in a peer review journal. I am personally not happy with the definition the researchers used to define castrate. To achieve the best results it is important to get the testosterone levels to below 25 ng/dl. There was no indication as to whether or not the subjects were actually able to achieve this level of testosterone. Primary source: 2009 Genitourinary Cancers Symposium Source reference: Langley RE, et al "PATCH, a randomized phase II trial of estrogen patches versus LHRH as first-line hormonal therapy for prostate cancer: planned interim analysis results" ASCO: GU 2009; Abstract 173. Joel T Nowak, MA, MSW[/fusion_builder_column][/fusion_builder_row][/fusion_builder_container]