Docetaxel and mitoxantrone can be combined safely as chemotherapy prior to radical prostatectomy for high-risk prostate cancer, according to a study.

In addition, the study demonstrated that it is feasible to administer chemotherapy with multiple agents before radical prostatectomy, with encouraging five-year survival, investigators reported in Cancer (2010; published online ahead of print).

Research has shown that the two chemotherapy agents are active in advanced prostate cancer. The drugs exert antitumor effects though distinct cellular mechanisms. Consequently, combining them has potential for synergistic activity against prostate cancer.

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In a phase 1/2 study, researchers led by Mark Garzotto, MD, and Tomasz M. Beer, MD, of Oregon Health and Science University in Portland enrolled 57 patients (median age 63 years) with high-risk prostate cancer. The men had a 10-year minimum life expectancy and at least one of the following high-risk features: clinical stage T2c or surgically resectable T3a tumors, a serum PSA level of 15 ng/mL or higher, or a Gleason sum of 7 or higher.

Docetaxel was administered at a fixed dose of 35 mg/m2; mitoxantrone was dose escalated in the first 10 patients who received the agent at doses of 2 to 5 mg/m2, and was given at a dose of 4 mg/m2 in all remaining patients. Patients were to receive four 28-day cycles of chemotherapy, with docetaxel and mitoxantrone given as three weekly doses followed by a one-week break. Dexamethasone 4 mg was given orally 12 hours and one hour before treatment and 12 hours after treatment.

Of the 57 patients, 54 completed the four cycles and had surgery and two completed fewer than four cycles before undergoing surgery because of adverse drug effects. One patient was lost to follow-up. The researchers observed no change in testosterone levels with chemotherapy. Neutropenia was the most common treatment-related hematologic toxicity, occurring in 50% patients. Hyperglycemia was the most frequent nonhematologic toxicity, occurred in 33% of patients.

The median operative time was 4.3 hours and the median estimated blood loss was 900 mL. In the 54 patients who had four cycles of chemotherapy, surgeons attained negative surgical margins in 36 (67%). The researchers observed no pathologic complete responders.

The postoperative PSA level was below 0.2 ng/mL in 43 patients (80%). After a median follow-up of 63 months, cancer recurred in 27 (47.4%) of the 57 patients enrolled in the study. The five-year recurrence-free survival for the entire study population was 49.8%. Among lymph node-negative patients, five-year recurrence-free survival was 58.7%.

The researchers detected lymph node involvement in 18.5% of cases. Lymph node involvement was the strongest independent predictor of early recurrence, the authors noted. Other predictors included pretreatment serum PSA level and post-chemotherapy tissue vascular endothelial growth factor expression.