Us TOO University Presents:
Estrogen Deficiency Side Effects Due to Androgen Deprivation Therapy.

This free webinar/teleconference with speaker Samir Taneja MD will
take place Wednesday, September 23, 2009, at 8pm Eastern,
7pm Central, 6pm Mountain, 5pm Pacific.

For more information and to RSVP today, go to:
http://www.ustooevents.org/site/Survey?ACTION_REQUIRED=URI_ACTION_USER_REQUESTS&SURVEY_ID=2700

Androgen-deprivation therapy is well-established for treating prostate cancer but is associated with bone loss and an increased risk of fracture. Matthew R. Smith and an international team investigated the effects of denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor-{kappa}B ligand, on bone mineral density and fractures in men receiving androgen-deprivation therapy for nonmetastatic prostate cancer. In today’s New England Journal of Medicine, August 20, they report positive results:

Princeton, New Jersey; July 9, 2009 — Sandoz today announced the introduction of bicalutamide tablets, USP a generic equivalent of Casodex®, in the United States. Bicalutamide is an androgen receptor inhibitor indicated for use in combination therapy with a luteinizing hormone-releasing hormone (LHRH) analog for the treatment of Stage D2 metastatic carcinoma of the prostate.

According to IMS Health, US sales for branded bicalutamide tablets, USP were approximately USD 319 million for the twelve months ending April 2009. Sandoz will market bicalutamide in 50mg strength tablets, the same as Casodex®.

On December 24, 2008 the US Food & Drug Administration granted tentative approval to Accord Healthcare’s bicalutamide.

Accord is a subsidiary of Intas Pharmaceuticals, Ltd., an Indian company. Accord’s function is licensing and marketing.

Below are a graph and a table of the effect of Ferring’s degarelix on testosterone compared with the effect of Lupron. On December 24th Ferring announced that FDA has approved degarelix for the treatment of hormonally sensitive advanced prostate cancer.

Degarelix (generic name) is a GnRH receptor antagonist. The company says: “Degarelix achieves medical castration differently than LHRH agonists, specifically by binding reversibly to GnRH receptors on cells in the pituitary gland, quickly reducing the release of gonadotropins and consequently testosterone.” How quickly? Like this :

Degarelix versus Lupron Effect: Percent drop in Testosterone drop over 28 days

Androgen deprivation therapy, heavily-prescribed for men with prostate cancer, may have an unforeseen downside. According to a new study, lack of androgen may make any surviving cancer cells more invasive.

Cougar Biotechnology’s once-daily oral drug CB7630 (abiraterone acetate), based on recently announced trial results, appears o have some efficacy at two stages of the standard treatment path for androgen independent prostate cancer — either before or after chemotherapy.

A UK Phase I/II trial of CB7630 reports positive signs among a small number of patients enrolled so far in a trial for AIPC men who have never taken chemotherapy but have taken LHRH analogues and multiple other hormonal therapies, including antiandrogens, diethylstilboestrol and dexamethasone. In addition, a Phase II trial ongoing at several US centers and in the UK indicates that CB7630 may benefit some patients who have used up Taxotere (docetaxel) chemotherapy.

CB7630 (abiraterone acetate) is reported to have “minimal toxicity” (as yet no maximum tolerated dose has been reached). Among the small numbers of patients treated so far, benefits include lowering of PSA’s, some tumor shrinkage, and some pain reduction. In one of the trials, out of “20 evaluable patients with measurable tumor lesions, treatment with CB7630 resulted in partial radiological responses (as measured
by the RECIST criteria) in 11 patients (55%), with 7 patients demonstrating ongoing stable disease and 3 patients experienced regressing bone disease.”

The company says CB7630 “has the potential to be used by both urologists who treat patients with second line hormonal therapies and by medical oncologists who treat patients in the second line chemotherapy setting…” To that end, the company chose to announce results at AACR, aiming the presentation toward oncologists, and again at AUA:

Cougar Biotechnology Announces Interim Phase II Results Confirm
Efficacy of CB7630 in Both Chemotherapy Naïve and Chemotherapy
Refractory Prostate Cancer Patients April 17 (posted May 31) 2007.

Cougar . . . Presentation of Positive CB7630 (abiraterone acetate)
Clinical Data at AUA Annual Meeting May 21 (posted May 31), 2007

For three UK and US trials ongoing see:
clinicaltrials.gov/ct/search?term=CB7630&submit=Search

Timing of Androgen Deprivation Therapy and its Impact on Cancer-specific Survival after Radical Prostatectomy: A Matched-cohort Analysis (Abstract 601)

Adjuvant androgen deprivation therapy (ADT) can improve survival following radiation therapy or radical prostatectomy. Researchers from the Mayo Clinic in Rochester, Minnesota conducted a study that focused on 6,401 patients who underwent radical prostatectomy between 1990 and 1999 with node-negative prostate cancer. Patients were divided into five groups: those who underwent ADT in the adjuvant setting; those with ADT initiated at PSA greater or equal to 0.4 ng/ml, ADT initiated at PSA greater or equal to 1 ng/ml. ADT initiated at PSA greater or equal to 2 ng/ml and ADT at systemic progression. Median follow-up for the cohort was 10 years.

The study found that patients who underwent adjuvant ADT experienced improved 10-year systematic progression-free survival (95 percent vs. 90 percent) and 10-year cancer-specific survival (98 percent vs. 95 percent) compared to patients who did not undergo adjuvant ADT. The results do not dictate whether the initiation of ADT at any other stage can impact survival, although the survival advantage was found to diminish if ADT is administered farther in the disease process. These findings do, however, support the immediate use of ADT in high-risk radical prostatectomy patients while suggesting the limitations of ADT in enhancing survival after prostate-specific antigen progression.

This abstract will be presented during Podium Session 20 on Sunday, May 20 2007 starting at 3:30 p.m.