THE “NEW” PROSTATE CANCER INFOLINK

Rathkopf et al. have reported the results of a phase II trial of docetaxel in combination with rapid androgen cycling in patients with progressive, non-castrate prostate cancer. Patients in this trial exhibited a high incidence of high-grade febrile neutropenia, making it unlikely that this form of treatment has potential in the management of patients with progressive, non-castrate disease.

The trial involved 100 non-castrate patients who had received ≤ 6 months of hormone therapy. Cohort 1 (62 patients) received six 28-day cycles of docetaxel (75 mg/m²), leuprolide, and 7 days of topical testosterone. Cohort 2 (38 patients) received nine 21-day cycles of docetaxel (70 mg/m²), leuprolide, and 3 days of testosterone. The primary end point was the percentage of patients who achieved non-castrate testosterone levels (> 150 ng/dL) and an undetectable PSA level (≤ 0.05, ≤ 0.5, or ≤ 2.0 ng/mL with prior prostatectomy, radiation therapy, or no definitive therapy, respectively) at 18 months. 

The results of the study were as follows:

• A higher proportion of patients in cohort 2 achieved the undetectable PSA outcome at 18 months relative to cohort 1 (13 vs 0 percent).
• There was a 16% incidence of febrile neutropenia among all patients, which was higher than that observed in patients with castration-resistant disease. This may have been related to a 50 percent reduction in overall docetaxel clearance in the non-castrate group.
• There was no alteration in CYP3A4 activity (P = 0.87) or docetaxel clearance (P = 0.88) between cycles.

The authors concluded that:

• The undetectable PSA end point does allow for a rapid screening of interventions, which may have value in further studies.
• Increasing the number of docetaxel cycles after a shorter period of testosterone repletion, and a longer duration of testosterone depletion, increased the proportion of men who achieved an undetectable PSA.
• The higher-than-expected incidence of febrile neutropenia may have been related to the reduced overall docetaxel clearance in patients with non-castrate versus castrate testosterone levels.