Chemohormonal therapy did not improve survival for metastatic prostate cancer

The addition of ketoconazole and doxorubicin alternated with vinblastine and estramustine to standard androgen deprivation therapy increased treatment-related adverse events, according to data from a phase-3 trial.

Researchers examined the role of alternating chemotherapy plus sustained androgen ablation among 286 patients with metastatic prostate cancer. All patients were assigned to androgen ablation therapy, and 137 patients were assigned to three cycles of ketoconazole and doxorubicin alternated with vinblastine and estramustine (Emcyt, Pharmacia/Upjohn). Chemotherapy was repeated every eight weeks. The primary endpoint was time to castrate-resistant progression.

Eighty percent of patients in the experimental arm completed all three cycles of therapy. Those who discontinued therapy reported fatigue and thromboembolic events.

In the standard therapy arm, median time to progression was 24 months compared with 35 months in the experimental arm. Median follow-up was 6.4 years, at which time OS was 5.4 years for standard therapy and 6.1 years for experimental therapy.

According to the researchers, PSA kinetics at the time of androgen therapy and the nadir after hormone treatment were related to survival.

Chemotherapy increased treatment-related adverse events; 51% of patients exposed to chemotherapy had at least one grade-3 event, and most were considered related to treatment. Nine percent of patients in the standard therapy arm experienced at least one grade-3 event, of which most were considered unrelated to treatment.

“These data are consistent with at least 10 previous randomized trials of chemohormonal therapy in providing no support for adding cytotoxics to androgen ablation for androgen-driven prostate cancer,” the researchers wrote.

J Clin Oncol. 2008;doi:10.1200/JCO.2007.15.9830.