Neoadjuvant Docetaxel and Capecitabine in Patients With High Risk Prostate Cancer

Purpose: Docetaxel is the most active cytotoxic agent in hormone refractory prostate cancer. Preclinically docetaxel increases expression of thymidine phosphorylase, an enzyme responsible for activation of capecitabine to 5-fluorouracil resulting in increased antitumor activity. We assessed activity and safety of neoadjuvant docetaxel and capecitabine in patients with high risk prostate cancer. Materials and Methods: Patients with either clinical stage greater than T2, prostate specific antigen 15 ng/ml or more, or Gleason sum 8 or greater received 3 to 6 cycles of docetaxel (36 mg/m² intravenously on days 1, 8 and 15) and capecitabine (1,250 mg/m² per day orally divided twice a day on days 5 to 18) every 28 days, followed by local therapy. The primary end point was rate of 50% or greater prostate specific antigen decrease. Correlative studies included qualitative changes in histology, tissue thymidine phosphorylase and survivin expression, and CK18Asp396 (serum apoptosis marker). Results: A total of 15 patients were treated, of whom 6 (40%) experienced a 50% or greater decrease in prostate specific antigen with infrequent diarrhea or hand-foot syndrome. Eleven patients underwent radical prostatectomy. There were no pathological complete responses and 4 patients demonstrated mild histological changes, including focal necrosis and vacuolated cytoplasm. While there was no discernable pattern of increased thymidine phosphorylase expression, 4 specimens showed decreased survivin expression, suggesting a possible mechanism for chemotherapy induced apoptosis. There was no correlation of prostate specific antigen response and survivin expression, and no increase in serum CK18Asp396. Conclusions: Neoadjuvant docetaxel and capecitabine is well tolerated but is not associated with significant pathological and prostate specific antigen responses.