Phase II Trial of Neoadjuvant Nab-Paclitaxel in High Risk Patients With Prostate Cancer Undergoing Radical Prostatectomy

Purpose: Taxane based chemotherapy has activity in advanced prostate cancer but previous studies of neoadjuvant docetaxel demonstrated a prostate specific antigen response with no obvious antitumor activity. The efficacy and safety of neoadjuvant albumin-bound paclitaxel (nab-paclitaxel, Abraxane(R)), a novel nanoparticle based formulation, were assessed in patients with high risk, locally advanced prostate cancer. Materials and Methods: Eligible patients had locally advanced prostatic adenocarcinoma, clinical stage cT2b or greater, Gleason score 8 or greater, or serum prostate specific antigen 15 ng/ml or greater without metastatic disease. Patients received 2 cycles of 150 mg/m(2) nab-paclitaxel weekly for 3 weeks during each 4-week cycle, followed by radical prostatectomy with bilateral lymphadenectomy. Efficacy assessments included pathological and prostate specific antigen response. Results: A total of 19 patients completed neoadjuvant therapy and 18 underwent radical prostatectomy. Median pretreatment prostate specific antigen was 8.5 ng/ml and median Gleason score was 8. Despite the lack of complete pathological responses 5 of 18 patients (28%) had organ confined disease and 9 of 18 (50%) had specimen confined disease. Post-chemotherapy prostate specific antigen was decreased in 18 of 19 (95%) patients and median decrease was 2.9 ng/ml (35%, p <0.001). An initial prostate specific antigen after radical prostatectomy of 0.02 ng/ml or less was achieved in 17 of 18 (94%) patients. There were no significant perioperative complications. Cytoplasmic vacuolization (focal in 10 and extensive in 7) was evident in all but 1 patient (94%). Ten patients (56%) had grade 3 and 1 had grade 4 neutropenia with no febrile neutropenia. Conclusions: Neoadjuvant nab-paclitaxel was well tolerated. Similar to our experience with neoadjuvant docetaxel there were no pathological complete responses, although a possible histological antitumor effect was observed.