Pre-op Chemotherapy Could Aid Prostate Cancer Treatment

Renal and Urology News | 10.22.2009

Preoperative combination chemotherapy with docetaxel and mitoxantrone appears to be safe, and about 50% of men with high-risk localized prostate cancer remain relapse-free at five years with this treatment regimen, according to new data presented at the American Society of Clinical Oncology Annual Meeting.

Docetaxel and mitoxantrone have been shown to have antitumor effects through distinct cellular mechanisms. Researchers have theorized that delivering a combination of these agents prior to surgery may benefit men with high-risk prostate cancer. Investigators now have five-year outcome data for 57 patients (mean age 62 years, range 49-74 years) treated with a novel regimen that combines these agents without androgen suppression therapy prior to prostatectomy. They also examined pathologic and clinical predictors of early relapse.

Subjects received weekly docetaxel 35 mg/m2 and mitoxantrone (escalated up to 4 mg/m2) for three of every four weeks per cycle for a total of four cycles over 16 weeks. The men then underwent radical prostatectomy. The primary study end point was biochemical relapse-free survival. Biochemical relapse was defined as a confirmed PSA level greater than 0.4 ng/mL.

Of the 57 patients, 54 received all four cycles of docetaxel plus mitoxantrone prior to radical prostatectomy. Grade 4 toxicities were limited to leukopenia, neutropenia, and hyperglycemia. Serum testosterone levels remained stable after chemotherapy. In 67% of cases, negative surgical margins were attained; lymph node involvement was detected in only 18.5%. Twenty-seven of the 57 patients (47.4%) experienced disease recurrence; median follow-up was 63 months (range 7-86 months).

Progression-free survival was 65.5% and 49.8% at two and five years, respectively. Pretreatment serum PSA, lymph node involvement, and postchemotherapy tissue expression of vascular endothelial growth factor (VEGF) were independent predictors of early relapse.

“We are finding that about half of the patients five years out are still disease-free,” said investigator Tomasz Beer, MD, Professor of Urology at Oregon Health & Science University in Portland. “One of the interesting [findings] was that VEGF expression was an important predictor of relapse. That is exciting for the field because drugs that target VEGF may be on the right track.”

Preoperative chemotherapy is still considered an area of experimentation, but Dr. Beer said the new findings justify prospective, large-scale studies.

 Copyright Renal and Urology News 2009