title: Intraperitoneal chemotherapy for the initial management of primary epithelial ovarian cancer.
abstract: BACKGROUND
  Ovarian cancer tends to be chemosensitive and confine itself to the surface of the peritoneal cavity for much of its natural history. These features have made it an obvious target for intraperitoneal (IP) chemotherapy. Chemotherapy for ovarian cancer is usually given as an intravenous (IV) infusion repeatedly over five to eight cycles. Intraperitoneal chemotherapy is given by infusion of the chemotherapeutic agent directly into the peritoneal cavity. There are biological reasons why this might increase the anticancer effect and reduce some systemic adverse effects in comparison to IV therapy.
  
  
  OBJECTIVE
  To determine if adding a component of the chemotherapy regime into the peritoneal cavity affects overall survival, progression-free survival, quality of life (QOL) and toxicity in the primary treatment of epithelial ovarian cancer.
  
  
  METHODS
  We searched the Gynaecological Cancer Review Group's Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 2, 2011, MEDLINE (1951 to May 2011) and EMBASE (1974 to May 2011). We updated these searches in February 2007, August 2010, May 2011 and September 2015. In addition, we handsearched and cascade searched the major gynaecological oncology journals up to May 2011.
  
  
  METHODS
  The analysis was restricted to randomised controlled trials (RCTs) assessing women with a new diagnosis of primary epithelial ovarian cancer, of any FIGO stage, following primary cytoreductive surgery. Standard IV chemotherapy was compared with chemotherapy that included a component of IP administration.
  
  
  METHODS
  We extracted data on overall survival, disease-free survival, adverse events and QOL and performed meta-analyses of hazard ratios (HR) for time-to-event variables and relative risks (RR) for dichotomous outcomes using RevMan software.
  
  
  RESULTS
  Nine randomised trials studied 2119 women receiving primary treatment for ovarian cancer. We considered six trials to be of high quality. Women were less likely to die if they received an IP component to chemotherapy (eight studies, 2026 women; HR = 0.81; 95% confidence interval (CI): 0.72 to 0.90). Intraperitoneal component chemotherapy prolonged the disease-free interval (five studies, 1311 women; HR = 0.78; 95% CI: 0.70 to 0.86). There was greater serious toxicity with regard to gastrointestinal effects, pain, fever and infection but less ototoxicity with the IP than the IV route.
  
  
  CONCLUSIONS
  Intraperitoneal chemotherapy increases overall survival and progression-free survival from advanced ovarian cancer. The results of this meta-analysis provide the most reliable estimates of the relative survival benefits of IP over IV therapy and should be used as part of the decision making process. However, the potential for catheter related complications and toxicity needs to be considered when deciding on the most appropriate treatment for each individual woman. The optimal dose, timing and mechanism of administration cannot be addressed from this meta-analysis. This needs to be addressed in the next phase of clinical trials.
authors.affiliation: Ward K3 John Hunter Hospital, Hunter New England Centre for Gynaecological Cancer, Locked Bag 1, Hunter Regional Mail Centre, Newcastle, New South Wales, Australia, 2310.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Jaaback
authors.forename: Nick
authors.initials: N
authors.lastname: Johnson
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Lawrie
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy / Q000009:adverse effects / Q000379:methods*; D007262:Infusions, Intravenous; D007263:Infusions, Parenteral / Q000009:adverse effects / Q000379:methods*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D016032:Randomized Controlled Trials as Topic
chemical_list: D000970:Antineoplastic Agents