title: Phase II trial of neoadjuvant docetaxel and gefitinib followed by radical prostatectomy in patients with high-risk, locally advanced prostate cancer.
abstract: BACKGROUND
  Prostate cancer trials investigating neoadjuvant hormonal therapy, followed by surgery, have demonstrated that elimination of all tumor cells from the primary site is rare. The authors report a phase 2 trial assessing the efficacy and toxicity of docetaxel and gefitinib in patients with high-risk localized prostate cancer as neoadjuvant therapy before radical prostatectomy (RP).
  
  
  METHODS
  Thirty-one patients with high-risk prostate cancer were treated with docetaxel and gefitinib for 2 months before RP. All patients met the criteria of clinical stage T2b-3 or serum prostate-specific antigen (PSA) level >20 ng/mL, or Gleason score of 8 to 10. The primary endpoint was pathologic complete response. Secondary objectives included clinical response. When available, endorectal coil magnetic resonance imaging (eMRI) was performed as part of clinical response evaluation. Immunohistochemical staining of epidermal growth factor receptor and HER-2/neu was performed on prechemotherapy and postchemotherapy prostate tissue.
  
  
  RESULTS
  The median age of the patients was 60 years, the median pretreatment PSA level was 7.43 ng/mL, and the median Gleason score was 8. Clinical staging prior to treatment consisted of: T1 in 4 patients, T2 in 17 patients, and T3 in 10 patients. One patient with enlarged pelvic adenopathy and T4 disease did not undergo RP. Thirty patients received all scheduled therapies including RP. Grade 3 toxicities included asymptomatic liver function test elevation in 4 (13%) patients, diarrhea in 1 (3%) patient, and fatigue in 1 (3%) patient. One patient experienced grade 4 toxicity with elevated alanine aminotransferase. RP specimen pathology demonstrated residual carcinoma in all cases. Twenty-nine (94%) patients achieved a clinical partial response, including 35% of patients who demonstrated radiographic improvement on eMRI.
  
  
  CONCLUSIONS
  No pathologic complete response was noted in 31 patients treated with docetaxel and gefitinib. This combination was well tolerated, and did not result in increased surgical morbidity.
authors.affiliation: Section of Hematology/Oncology, Virginia Mason Medical Center, Seattle, Washington 98101, USA. jacqueline.vuky@vmmc.org
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Vuky
authors.forename: Christopher
authors.initials: C
authors.lastname: Porter
authors.forename: Christina
authors.initials: C
authors.lastname: Isacson
authors.forename: Matthew
authors.initials: M
authors.lastname: Vaughan
authors.forename: Paul
authors.initials: P
authors.lastname: Kozlowski
authors.forename: Vincent
authors.initials: V
authors.lastname: Picozzi
authors.forename: John
authors.initials: J
authors.lastname: Corman
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D000077143:Docetaxel; D005500:Follow-Up Studies; D000077156:Gefitinib; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery*; D011799:Quinazolines / Q000008:administration & dosage; D012307:Risk Factors; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D011799:Quinazolines; D043823:Taxoids; D000077143:Docetaxel; D000077156:Gefitinib