title: Clinical and biological effects of neoadjuvant sargramostim and thalidomide in patients with locally advanced prostate carcinoma.
abstract: OBJECTIVE
  Granulocyte macrophage colony-stimulating factor (GM-CSF) and thalidomide are active agents in prostate cancer. This study assessed the biological effects and safety of GM-CSF and thalidomide in patients with localized prostate cancer before radical prostatectomy.
  
  
  METHODS
  Locally advanced prostate cancer patients undergoing radical prostatectomy were recruited for this study. Treatment consisted of two 28-day cycles of GM-CSF (250 microg, s.c., thrice weekly) and thalidomide (200 mg, orally, daily) on days 1 to 28 of each cycle. Radical prostatectomy occurred within 7 to 10 days after completion of therapy. Pretreatment and posttreatment specimens were used to assess the expression of CD3, CD68, Ki-67, S100, PTEN, and CD31. Peripheral blood was examined for dendritic cells, regulatory T cells, and cytokines.
  
  
  RESULTS
  Twenty-eight patients were enrolled. No pathologic responses (P0) were observed and no unexpected toxicities or surgical complications occurred. Eighty-one percent of patients had a prostate-specific antigen decline (mean +/- SD decrease was 21.1 +/- 15.4%; median, 18.0%). With a median follow-up of 32 months, five patients have experienced progression. Radical prostatectomy tumor tissue specimens showed significant CD3 and S100 overexpression when compared with pretreatment biopsies. No significant changes in tumor macrophage infiltration were observed. Increased number of serum dendritic cell, as well as high serum levels of interleukin-8, basic fibroblast growth factor, and vascular endothelial growth factor, was also observed.
  
  
  CONCLUSIONS
  Neoadjuvant GM-CSF and thalidomide was safe and feasible and did not affect the perioperative morbidity of radical prostatectomy. Although no pathologic complete responses were observed, significant posttreatment tumor T-cell and dendritic cell infiltration was noted. No significant changes in serum cytokines, dendritic cells, or regulatory T cells were induced.
authors.affiliation: Department of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio 44195, USA. Garciaj4@ccf.org
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Garcia
authors.forename: Eric A
authors.initials: EA
authors.lastname: Klein
authors.forename: Cristina
authors.initials: C
authors.lastname: Magi-Galluzzi
authors.forename: Paul
authors.initials: P
authors.lastname: Elson
authors.forename: Pierre
authors.initials: P
authors.lastname: Triozzi
authors.forename: Robert
authors.initials: R
authors.lastname: Dreicer
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D017430:Prostate-Specific Antigen / Q000097:blood / Q000187:drug effects; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000601:surgery; D011994:Recombinant Proteins; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects; D046888:Tissue Array Analysis
chemical_list: D011994:Recombinant Proteins; D013792:Thalidomide; C081222:sargramostim; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D017430:Prostate-Specific Antigen