A Canadian group has reported early results from the use of docetaxel + androgen deprivation therapy given prior to radical prostatectomy in an attempt to lower the risk of disease progression post-surgery in men with high-risk, localized prostate cancer.
Newly diagnosed patients enrolled in this phase II, multicenter study had to have untreated, clinically localized prostate cancer and certain high risk features. All patients were treated with androgen deprivation therapy (6.3 mg buserelin acetate every 8 weeks for three doses and an antiandrogen for 4 weeks) with docetaxel (35 mg/m2 weekly for 6 of 8 weeks for three doses).
A total of 72 men with a median age of 59 years (range 46 to 78) were enrolled in the study. Baseline characteristics included:
- Clinical stage T1c (14 percent), T2 (47 percent) or T3 (39 percent)
- Gleason score ≤7 (40 percent), 8 (29 percent) and 9 (31 percent)
- Median baseline prostate specific antigen of 10.8 ng/mL (range 1.6 to 65.6)
Eight patients did not complete protocol therapy because of toxicity (4), withdrawal of consent (1) and other reasons (3). For the 64 patients completing protocol therapy, results may be summarized as follows:
- Two patients had a complete pathological response (in other words, there was no sign of cancer in the prostate tissue post surgery).
- Pathological stage was T2 in 53 percent and T3 in 44 percent of patients.
- Four patients had N1 disease
- Positive surgical margins were identified in 27 percent of patients.
- At a median follow-up of 42.7 months (range 25.6 to 65.6) 19 patients (30 percent) had disease relapse.
The authors conclude that combined androgen deprivation and docetaxel given prior to radical prostatectomy was feasible, and resulted in encouraging recurrence-free survival. They further state that while pathological down staging was observed, pathological complete response rates were rare.
The “New” Prostate Cancer InfoLink considers that these preliminary results of aggressive therapy prior to surgery are interesting. However, a great deal of additional data will be needed before the use of such therapy becomes compelling. A key question surrounds the number of men included in this study who had Gleason scores of ≤ 7. If these were patients with cancer entirely localized to the prostate, it is not clear to us why they would have been included in this trial.
At this time, we would suggest, trials of this form of therapy need to be carried out in two different groups of patients. We would suggest that Group A can be defined as patients who have Gleason scores of 4 + 3 = 7 and higher and clinical stage T2b-T3 disease. Group B would be characterized by patients with Gleason scores of 3 + 4 = 7 and lower, together with other high risk characteristics such as T3 disease or a significantly elevated PSA level. These two patient groups would seem to us to fall into somewhat different risk categories.
Filed under: Drugs in development, Management, Treatment
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