Weekly Neoadjuvant Ixabepilone on Surgical Feasibility and Clinical Outcomes in Locally Advanced High-Risk Prostate Cancer: A Phase II Clinical Trial
Keywords:Ixabepilone, prostate cancer, neoadjuvant chemotherapy, taxanes, epothilone.
Background:Men diagnosed with locally advanced high-risk prostate cancer have up to a 40% risk of biochemical recurrence after prostatectomy. The authors performed a phase II trial of neoadjuvant weekly ixabepilone prior to radical prostatectomy.
Methods:Enrollment criteria included patients with high-risk prostate cancer defined by D¢‚¬„¢Amico criteria or high-volume Gleason 4+3 with a palpable nodule. Patients received ixabepilone 20 mg/m2/week or 16 mg/m2/week for 3 weeks every 28 days for 4 cycles followed by surgery 2-8 weeks later.
Results:Sixteen patients were enrolled with a mean age of 56.5 years (range 43-70). PSA values decreased by a mean of 47% in 14/16 men with patients receiving a mean of 8.25 weeks of treatment (range 2-12). Nine men experienced an adverse event requiring dose modification or premature cessation of chemotherapy. Pathologic staging in 9 patients showed T3a, 5 with T3b, and 1 with T2c disease; 8 had R1 disease and 2 demonstrated nodal involvement. Mean operative time, blood loss, and hospital stay were 189 minutes, 184 mL, and 1.5 days, respectively. At median follow-up of 32 months (range 15-45), 4 patients experienced biochemical recurrence.
Conclusions: Neoadjuvant weekly ixabepilone had a good PSA response and no increased surgical morbidity; however, a higher dose is associated with significant persistent neuropathy. There were no complete pathologic responses, but biochemical recurrence rate is low. Further assessment of time to treatment failure will require continued, planned follow-up to evaluate the long-term potential clinical benefit of this study.
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