title: Phase III multicenter clinical trial of the sialyl-TN (STn)-keyhole limpet hemocyanin (KLH) vaccine for metastatic breast cancer.
abstract: OBJECTIVE
  This double-blind, randomized, phase III clinical trial evaluated time to progression (TTP) and overall survival in women with metastatic breast cancer (MBC) who received sialyl-TN (STn) keyhole limpet hemocyanin (KLH) vaccine. Secondary endpoints included vaccine safety and immune response.
  
  
  METHODS
  The study population consisted of 1,028 women with MBC across 126 centers who had previously received chemotherapy and had had either a complete or a partial response or no disease progression. All women received one-time i.v. cyclophosphamide (300 mg/m(2)) 3 days before s.c. injection of 100 μg STn-KLH plus adjuvant (treatment group) or 100 μg KLH plus adjuvant (control group) at weeks 0, 2, 5, and 9. Subsequently, STn-KLH without adjuvant or KLH without adjuvant was then administered monthly for 4 months, and then quarterly until disease progression, without cyclophosphamide.
  
  
  RESULTS
  STn-KLH vaccine was well tolerated; patients had mild to moderate injection-site reactions and reversible flu-like symptoms. Week-12 antibody testing revealed high specific IgG titers and a high rate of IgM-to-IgG seroconversion; the median IgG titers in STn-KLH recipients were 320 (anti-ovine submaxillary mucin) and 20,480 (anti-STn), with no detectable antimucin antibodies in the control group. The TTP was 3.4 months in the treatment group and 3.0 months in the control group. The median survival times were 23.1 months and 22.3 months, respectively.
  
  
  CONCLUSIONS
  Although STn-KLH was well tolerated in this largest to date metastatic breast cancer vaccine trial, no overall benefit in TTP or survival was observed. Lessons were learned for future vaccine study designs.
authors.affiliation: Mount Vernon Cancer Center, Northwood, Middlesex, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Miles
authors.forename: Henri
authors.initials: H
authors.lastname: Roché
authors.forename: Miguel
authors.initials: M
authors.lastname: Martin
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Perren
authors.forename: David A
authors.initials: DA
authors.lastname: Cameron
authors.forename: John
authors.initials: J
authors.lastname: Glaspy
authors.forename: David
authors.initials: D
authors.lastname: Dodwell
authors.forename: Joanne
authors.initials: J
authors.lastname: Parker
authors.forename: José
authors.initials: J
authors.lastname: Mayordomo
authors.forename: Alejandro
authors.initials: A
authors.lastname: Tres
authors.forename: James Lee
authors.initials: JL
authors.lastname: Murray
authors.forename: Nuhad K
authors.initials: NK
authors.lastname: Ibrahim
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000912:Antibodies, Neoplasm / Q000097:blood; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006433:Hemocyanins / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C099077:sialyl-Tn antigen-keyhole-limpet hemocyanin conjugate; D003520:Cyclophosphamide; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin