title: Phase II trial of neoadjuvant docetaxel and CG1940/CG8711 followed by radical prostatectomy in patients with high-risk clinically localized prostate cancer.
abstract: BACKGROUND
  Prostate cancer (PC) is the most commonly diagnosed noncutaneous malignancy in American men. PC, which exhibits a slow growth rate and multiple potential target epitopes, is an ideal candidate for immunotherapy. GVAX for prostate cancer is a cellular immunotherapy, composed of PC-3 cells (CG1940) and LNCaP cells (CG8711). Each of the components is a prostate adenocarcinoma cell line that has been genetically modified to secrete granulocyte-macrophage colony-stimulating factor. Hypothesizing that GVAX for prostate cancer could be effective in a neoadjuvant setting in patients with locally advanced disease, we initiated a phase II trial of neoadjuvant docetaxel and GVAX. For the trial, the clinical effects of GVAX were assessed in patients undergoing radical prostatectomy (RP).
  
  
  METHODS
  Patients received docetaxel administered at a dose of 75 mg/m(2) every 3 weeks for 4 cycles. GVAX was administered 2-3 days after chemotherapy preoperatively for four courses of immunotherapy. The first dose of GVAX was a prime immunotherapy of 5×10(8) cells. The subsequent boost immunotherapies consisted of 3×10(8) cells. After RP, patients received an additional six courses of immunotherapy. Pathologic complete response, toxicity, and clinical response were assessed. The primary endpoint of the trial was a pathologic state of pT0, which is defined as no evidence of cancer in the prostate.
  
  
  RESULTS
  Six patients completed neoadjuvant docetaxel and GVAX therapy. No serious drug-related adverse events were observed. Median change in prostate-specific antigen (PSA) following neoadjuvant therapy was 1.47 ng/ml. One patient did not undergo RP due to the discovery of positive lymph nodes during exploration. Of the five patients completing RP, four had a downstaging of their Gleason score. Undetectable PSA was achieved in three patients at 2 months after RP and in two patients at 3 years after RP.
  
  
  CONCLUSIONS
  Neoadjuvant docetaxel/GVAX is safe and well tolerated in patients with high-risk locally advanced PC. No evidence of increased intraoperative hemorrhage or increased length of hospital stay postoperatively was noted. These results justify further study of neoadjuvant immunotherapy.
authors.affiliation: Oregon Health and Science University, Portland, Oregon 97239-3098, USA. vukyja@ohsu.edu
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Vuky
authors.forename: John M
authors.initials: JM
authors.lastname: Corman
authors.forename: Christopher
authors.initials: C
authors.lastname: Porter
authors.forename: Semra
authors.initials: S
authors.lastname: Olgac
authors.forename: Evan
authors.initials: E
authors.lastname: Auerbach
authors.forename: Kathryn
authors.initials: K
authors.lastname: Dahl
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols; D014408:Biomarkers, Tumor; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000235:genetics; D045744:Cell Line, Tumor; D000077143:Docetaxel; D064420:Drug-Related Side Effects and Adverse Reactions / Q000473:pathology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D008297:Male; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D043823:Taxoids / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D019496:Cancer Vaccines; D043823:Taxoids; D000077143:Docetaxel; D016178:Granulocyte-Macrophage Colony-Stimulating Factor