The Friday news reports (Part A): February 13, 2009

After a relatively quiet news period, the flood gates have opened again, so we shall divide today’s news reports into two postings for easier reading. We have also published a separate report on the possibility of an association between alcohol use and prostate cancer diagnosis.

Studies have previously suggested that, in men with advanced prostate cancer, expression of a protein known as p63 may be helpful in distinguishing aggressive disease from less aggressive disease (in which expression of p63 is less evident). Dhillon et al. conducted a prospective study using tissue from 298 men (aged 51 to 84 years) who were diagnosed with prostate cancer in the Physicians’ Health Study between 1983 to 2004. They showed that high expression of p63 in the cytoplasm was associated with increased prostate cancer-specific mortality up to 20 years after diagnosis.

An article by Tretli et al. from Norway addresses the possibility that serum levels of 25-hydroxy-vitamin D are associated with prognosis in patients with prostate cancer. Their data suggests that medium or high serum levels of 25-hydroxy-vitamin D are significantly related to better prognosis compared with a low level. Analysis restricted to patients receiving hormone therapy gave a stronger association. They conclude that the serum level of  25-hydroxy-vitamin D may be involved in disease progression and is a potential marker of prognosis in patients with prostate cancer in this cohort of patients.

Van den Bergh et al. have attempted to determine whether  men newly diagnosed with Gleason 7 prostate cancer are appropriate as candidates for active surveillance (AS) instead of radical treatment. Active therapy was initially withheld in 50 men diagnosed with  Gleason 7 disease. Of these 50 patients, 29 (58 percent) would normally have been suitable for AS, as they had a PSA level of ≤10.0 ng/ml, a PSA density of < 0.2 , clinical stage T1c/T2 disease, and two or fewer positive biopsy-cores; 44 /50 (88 patients) had a Gleason score 3 + 4 = 7. The average age of the men was 69.5 years (range: 59.6-76.2). The 6-year cancer-specific survival (9 patients at risk) was 100 percent, which sharply contrasted with the 68 percent overall survival at 6 years. Men alive at the time of analysis had a favorable PSA level and PSA doubling time. The 6-year treatment-free survival was only 59 percent, with most patients switching to active therapy, justified on the basis of their PSA level. However, men with otherwise favorable tumor characteristics and a Gleason score of 3 + 4 = 7 remained treatment-free significantly longer than their counterparts with unfavorable tumour features and a Gleason score of 4 + 3 = 7. The authors conclude that, for selected patients with screen-detected Gleason 3 + 4 = 7 prostate cancer, AS may be an appropriate option, especially in those with comorbidity and/or a short life expectancy.

Mellado et al. have reviewed data on the potential mechanisms of development of resistance to androgen deprivation therapy (ADT) and the possibility that castration-resistant prostate cancer cells may still depend on androgen receptor (AR) signaling for growth. They describe five different mechanisms that can enhance AR signalling in an androgen-depleted environment and identify multiple novel agents  targeting the AR signalling pathway that are currently in development, including more effective antiandrogens; inhibitors of CYP17, inhibitors of HSP90, inhibitors of histone deacetylases, and inhibitors of tyrosine kinase inhibitors.

VIVUS, Inc. has announced the initiation of the second of four pivotal Phase 3 trials of avanafil, an investigational new drug for the treatment of erectile dysfunction (ED). Avanafil is a  fast-acting, selective, investigational oral phosphodiesterase type 5 (PDE5) inhibitor. According to an earlier media release, one of these four studies will specifically enroll patients with ED in a 16-week randomized, controlled trial subsequent to radical prostatectomy. However, that study is not expected to start enrolling patients until later in 2009.

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