Docetaxel in high-risk disease

A new randomized, phase III clinical trial published in Lancet Oncology reports that administration of estramustine plus docetaxel together with androgen deprivation therapy (ADT) is associated with improved relapse-free survival over ADT alone in patients with high-risk, localized prostate cancer.

The combination of docetaxel and estramustine has been shown to improve survival in patients with castration-resistant prostate cancer, so Fizazi and co-workers decided to test its efficacy in patients with high-risk, treatment-naive, localized prostate cancer. The researchers randomly assigned patients to receive either ADT alone (goserelin 10.8 mg every 3 months for 3 years; n = 206) or to ADT plus four cycles of docetaxel (70 mg/m²) on day 2 and estramustine (10 mg/kg per day) on days 1–5, every 3 weeks (n = 207).

Over a median follow-up duration of 8.8 years (interquartile range 8.1–9.7 years), 88 patients (43%) in the ADT plus docetaxel and estramustine group had a relapse or died compared with 111 patients (54%) in the ADT-alone group. Biochemical failure was the most common first relapse event, occurring in 130 (65%) of 199 patients, with similar numbers in each group.

At 8 years, relapse-free survival was 62% in the ADT plus docetaxel and estramustine group compared with 50% in the ADT-alone group (adjusted hazard ratio 0.71; 95% CI 0.54–0.94; P = 0.017).

The authors report no treatment-related deaths, and rates of grade 2 or higher adverse events were similar in the two groups. Rates of second cancers were also similar in the two groups, with an 8-year cumulative incidence of 11% in the ADT plus docetaxel and estramustine group versus 10% in the ADT-alone group (P = 0.57).

“In conclusion, adding docetaxel and estramustine to ADT significantly improved recurrence-free survival compared with ADT alone in patients with high-risk localised prostate cancer, with no apparent long-term toxicity related to chemotherapy,” say the authors. “Longer follow-up will be needed to establish whether this benefit translates into improved metastasis-free survival, and ultimately, overall survival.”