Phase I study of weekly mitoxantrone and docetaxel before prostatectomy in patients with high-risk localized prostate cancer.

Purpose: The purpose is to determine the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of mitoxantrone and docetaxel administered weekly before prostatectomy in men with localized prostate cancer at high risk for recurrence.

Experimental Design: Twenty-two patients were treated with four cycles of docetaxel 35 mg/m(2) and increasing doses of mitoxantrone starting at 2 mg/m(2) repeated weekly for 3 weeks of a 4-week cycle before prostatectomy. The MTD was defined as that dose at which fewer than one-third of patients experienced a DLT (>or=grade 4 hematological or >or=>grade 3 nonhematological toxicity). Changes in serum prostate-specific antigen and serum testosterone, and pathological outcome with surgery were secondary endpoints.

Results: The MTD for mitoxantrone in combination with this dose of docetaxel was 4 mg/m(2). Neutropenia was the DLT for the combination. Ten of 12 patients treated at the MTD completed the planned 16 weeks of chemotherapy, whereas 2 discontinued therapy early because of toxicity. The median reduction in PSA was 41% (range, 4-88%). Serum testosterone levels remained constant postchemotherapy.

Conclusions: In this patient population, the planned Phase II regimen is 4 mg/m(2) mitoxantrone and 35 mg/m(2) docetaxel weekly for 3 of every 4 weeks. Delivery of this regimen before prostatectomy is feasible with acceptable toxicity. Additional studies are needed to determine whether this combined modality approach will reduce cancer recurrence rates in this high-risk population. Because extent of disease and exposure to prior therapy may impact treatment tolerance these safety data may not be applicable to patients with advanced prostate cancer.