Low-dose DES in the management of CRPC


The value of low-dose diethylstilbestrol (DES) in the management of men with advanced and castration-resistant prostate cancer (CRPC) comes up as a regular topic for review and discussion. Before development of the LHRH agonists, DES was the most commonly used — and much studied — drug for the treatment of advanced (metastatic) prostate cancer.

The historic problem with DES has always been the risk of cardiovascular side effects, particularly when the drug was used at a dose of 5 mg/day. Studies carried out as long ago as the 1960s and early 1970s strongly suggested that this risk of cardiovascular side effects could be significantly reduced by the use of low-dose DES (at 1 mg/day). However, the original clinical trial of leuprolide acetate (using daily injections of Lupron) compared it to use of DES at 3 mg/day. (See this original study report.)

Not only did the original trials conclude that, “leuprolide offers an important alternative treatment that is therapeutically equivalent to and causes fewer side effects than DES for the initial systemic management of metastatic prostate cancer.” It rapidly became evident that there were financial benefits to physicians from prescribing LHRH agonists as opposed to DES. There has never been a large head to head study of low-dose DES at 1 mg/day versus any dose of an LHRH agonist.

A newly published study by Clemons et al. is based on a retrospective chart review of 63 patients with CRPC treated with low-dose DES at the University of Colorado. Data from all 63 patients were evaluable for safety, but only data from 58/63 patients (92 percent) were evaluable for efficacy. All 63 patients had CRPC despite prior antiandrogen withdrawal. The majority of these patients (49/63; 78 percent) had not received any forms of chemotherapy.

Here are the key study results:

  • 19/49 patients (39 percent) who had not previously received chemotherapy showed a PSA decrease of ≥ 50 percent.
    • The median time to progression (TTP) in these 19 patients was 30 weeks.
  • 16/49 patients (33 percent) who had not previously received chemotherapy showed a PSA decrease for < 50 percent.
    • The median TTP in these 14 patients was 16.4 weeks.
  • 14/49 patients (29 percent) who had not previously received chemotherapy had progressive disease by PSA testing.
    • The median TTP in these 14 patients was 6.9 weeks.
  • 3/9 patients who had already received chemotherapy demonstrated PSA responses.
  • There was a high PSA response rate among patients re-treated with low-dose DES after a “drug holiday.”
  • Adverse thromboembolic events included
    • Deep vein thrombosis (DVT) in 2 patients
    • Primary fibrinolysis syndrome in a single patient.
  • Additional adverse events included gynecomastia in 37/63 patients (59 percent).

The authors conclude that, “Low-dose DES is safe and effective in a modern cohort of men with CRPC despite antiandrogen treatment. Its potential role in the post-chemotherapy setting and the suggestion of efficacy on re-challenge merits additional consideration.”

It is clear that, even at low doses, DES is not a drug that should be used in treatment of prostate cancer patients with a history of heart disease. However, the potential of low-dose DES in other patients with progressive prostate cancer is not clear today. It is evident that low-dose DES is active in many men with CRPC prior to chemotherapy, and it may well have activity in selected patients post-chemotherapy. It’s actual value in such patients, however, is not well characterized.

3 Responses

  1. A timely message. I started taking DES on May 17, 2012. My PSA on May 15, 2012, was 98. I am very impressed but not sure what it means: Is the PSA merely suppressed; or is the lesion also reduced? Who can know? PSA had steadily increased from 35 on May 15, 2011. I have tried all kinds of remedies, none medically accepted, since then with no positive indications. I was about to embark on a totally macrobiotic diet when I started on DES. Next PSA is this Monday next. That should tell the tale. I have had all the standard tests and confirmed the prostate lesion. I may do the diet anyway as a precaution. I have faith that it works. I know, “faith” is a dangerous word.

    FS

  2. I forgot to add in my previous response that my PSA on June 11, 2012, after 3 weeks of taking DES, was 11.0, a 90% improvement in only 3 weeks. It had been 98.0 on May 15, 2012.

    Finally, for clarification, the DES dosage is one 2 mg tablet per day with two 350 mg aspirin per day, one morning and one evening, chewed.

    FS

  3. 5/1/2014
    What is your current PSA latest test and are you still taking DES?

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