THE "NEW" PROSTATE CANCER INFOLINK

According to Phase I/II clinical trial data published on Wednesday in the on-line version of the Journal of Clinical Oncology, 9/24 subjects in one of the abiraterone prostate cancer studies demonstrated a decrease in tumor size. Maybe this helps to explain why Johnson & Johnson is willing to pay over $900 million for the company.

Many of the data in this report have previously been presented at various conferences, but this is the first formal publication in a peer-reviewed journal. According to the abstract of the article by Attard et al.:

• It has previously been suggested that castration-resistant prostate cancer (CRPC) commonly remains hormone dependent.
• Abiraterone acetate is a potent, selective, and orally available inhibitor of CYP17, the key enzyme in androgen and estrogen biosynthesis.
• This trial studied the activity of abiraterone acetate in 54 castrate, chemotherapy-naive CRPC patients
• Phase II expansion of the trial in 42/54  patients was designed to investigate whether a dose of at 1,000 mg/d reduced the PSA level by ≥ 50 percent in at least 7 patients.
• Computed tomography scans every 12 weeks and circulating tumor cell (CTC) enumeration were performed.
• The trial included addition of dexamethasone 0.5 mg/d to suppress resistance to abiraterone.

The results of this trial showed that

• There was a PSA decline of ≥ 50 percent in 28/42 patients (67 percent) in Phase II of the trial.
• PSA declines of ≥ 90 percent were seen in 8/42 patients (19 percent).
• There was radiologic evidence of at least partial response in 9/24 patients (37.5 percent) in Phase II of the trial.
• The median time to PSA progression on abiraterone acetate alone for all phase II patients was 225 days.
• The addition of dexamethasone at disease progression reversed resistance in 18/54 patients treated in the trial (33 percent) regardless of prior treatment with dexamethasone.
• Pretreatment serum androgen and estradiol levels were associated with a probability of a PSA decline of  50 percent and with an extended time to disease progression on abiraterone acetate and dexamethasone.

The authors conclude that, in patients with castration-resistant but chemotherapy-naive prostate cancer, CYP17 blockade by abiraterone acetate results in declines in PSA and CTC counts and radiologic responses, confirming that progression of CRPC is still commonly driven by the active levels of certain hormones.

An additional report on this paper and comments from Johann de Bono, the lead investigator, can be found in a Reuters report, also published yesterday.