title: Antigen-specific active immunotherapy for ovarian cancer.
abstract: BACKGROUND
  Despite advances in chemotherapy, prognosis of ovarian cancer remains poor. Antigen-specific active immunotherapy aims to induce tumour-antigen-specific anti-tumour immune responses as an alternative treatment for ovarian cancer.
  
  
  OBJECTIVE
  To assess the feasibility of antigen-specific active immunotherapy for ovarian cancer. Primary outcomes are clinical efficacy and antigen-specific immunogenicity with carrier-specific immunogenicity and side effects as secondary outcomes.
  
  
  METHODS
  For the previous version of this review, a systematic search of the Cochrane Central Register of Controlled Trials (CENTRAL) 2009, Issue 3, Cochrane Gynaecological Cancer Group Specialized Register, MEDLINE and EMBASE databases and clinicaltrials.gov was performed (1966 to July 2009). We conducted handsearches of the proceedings of relevant annual meetings (1996 to July 2009).For this update of the review the searches were extended to October 2013.
  
  
  METHODS
  Randomised controlled trials (RCTs), as well as non-randomised non-controlled studies that included participants with epithelial ovarian cancer, irrespective of stage of disease, and treated with antigen-specific active immunotherapy, irrespective of type of vaccine, antigen used, adjuvant used, route of vaccination, schedule, and reported clinical or immunological outcomes.
  
  
  METHODS
  Two reviews authors independently performed the data extraction. Risk of bias was evaluated for RCTs according to standard methodological procedures expected by The Cochrane Collabororation or for non-RCTs using a selection of quality domains deemed best applicable to the non-randomised non-controlled studies.
  
  
  RESULTS
  Fifty-five studies were included (representing 3051 women with epithelial ovarian cancer). Response definitions showed substantial variation between trials, which makes comparison of trial results unreliable. Information on adverse events was frequently limited. Furthermore, reports of both RCTs and non-RCTs frequently lacked the relevant information necessary to assess risk of bias. Serious biases in most of the included trials can therefore not be ruled out.The largest body of evidence is currently available for CA-125 targeted antibody therapy (16 studies: 2339 participants). Non-RCTs of CA-125 targeted antibody therapy suggests increased survival in humoral and/or cellular responders. However, four large randomised placebo-controlled trials did not show any clinical benefit despite induction of immune responses in approximately 60% of participants.Other small studies targeting many different tumour antigens showed promising immunological results. As these strategies have not yet been tested in RCTs, no reliable inferences about clinical efficacy can be made. Given the promising immunological results, limited side effects and toxicity exploration of clinical efficacy in large well-designed RCTs may be worthwhile.
  
  
  CONCLUSIONS
  We conclude that despite promising immunological responses, no clinically effective antigen-specific active immunotherapy is yet available for ovarian cancer. Results should be interpreted cautiously as there was a significant lack of relevant information for the assessment of risk of bias in both RCTs and non-RCTs.
authors.affiliation: Obstetrics & Gynecology CB30, University Medical Center Groningen, University of Groningen, Hanzeplein 1, P.O. Box 30.001, Groningen, Netherlands, 9700 RB.
authors.forename: Ninke
authors.initials: N
authors.lastname: Leffers
authors.forename: Toos
authors.initials: T
authors.lastname: Daemen
authors.forename: Wijnand
authors.initials: W
authors.lastname: Helfrich
authors.forename: H Marike
authors.initials: HM
authors.lastname: Boezen
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Cohlen
authors.forename: Cornelis J M
authors.initials: CJ
authors.lastname: Melief
authors.forename: Hans W
authors.initials: HW
authors.lastname: Nijman
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D018394:CA-125 Antigen / Q000276:immunology; D000077216:Carcinoma, Ovarian Epithelial; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D005260:Female; D006801:Humans; D016233:Immunotherapy, Active / Q000009:adverse effects / Q000379:methods*; D058990:Molecular Targeted Therapy / Q000379:methods; D009375:Neoplasms, Glandular and Epithelial / Q000276:immunology / Q000628:therapy*; D010051:Ovarian Neoplasms / Q000276:immunology / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic
chemical_list: D000911:Antibodies, Monoclonal; D018394:CA-125 Antigen