title: Platinum versus platinum-combination chemotherapy in platinum-sensitive recurrent ovarian cancer: a meta-analysis using individual patient data.
abstract: BACKGROUND
  The majority of women with ovarian cancer develop recurrent disease. For patients with a platinum-free interval of >6 months, platinum-based chemotherapy is a treatment of choice. The benefit of platinum-based combination chemotherapy in randomized trials varies, and a meta-analysis was carried out to gain more secure information on the size of the benefit of this treatment.
  
  
  METHODS
  We initiated a systematic review and meta-analysis following a pre-specified protocol to determine whether combination chemotherapy is superior to single-agent platinum chemotherapy in women with relapsed platinum-sensitive ovarian cancer.
  
  
  RESULTS
  A total of five potentially eligible randomized trials were identified that had used combination-platinum chemotherapy versus single-agent platinum chemotherapy in women with relapsed platinum-sensitive ovarian cancer. For one trial (190 patients), adequate contact with the investigators could not be established. Therefore, four trials that randomly assigned 1300 patients were included, with a median follow-up of 36.1 months. Overall survival (OS) analyses were based on 865 deaths and demonstrated evidence for the benefit of combination-platinum chemotherapy (HR = 0.80; 95% CI, 0.64-1.00; P = 0.05). Progression-free survival (PFS) analyses were based on 1167 events and demonstrated strong evidence for the benefit of combination-platinum chemotherapy (HR = 0.68; 95% CI, 0.57-0.81; P < 0.001). There was no evidence of a difference in the relative effect of combination-platinum chemotherapy on either OS or PFS in patient subgroups defined by previous paclitaxel (Taxol) treatment (OS, P = 0.49; PFS, P = 0.66), duration of treatment-free interval (OS, P = 0.86; PFS, P = 0.48) or the number of previous lines of chemotherapy (OS, P = 0.21; PFS, P = 0.27).
  
  
  CONCLUSIONS
  In this individual patient data (IPD) meta-analysis, we have demonstrated that combination-platinum chemotherapy improves OS and PFS across all subgroups. This provides the strongest evidence to date of the benefit of combination-platinum over single-agent platinum.
authors.affiliation: UCL Cancer Trials Centre, London, UK.
authors.forename: F A
authors.initials: FA
authors.lastname: Raja
authors.forename: N
authors.initials: N
authors.lastname: Counsell
authors.forename: N
authors.initials: N
authors.lastname: Colombo
authors.forename: J
authors.initials: J
authors.lastname: Pfisterer
authors.forename: A
authors.initials: A
authors.lastname: du Bois
authors.forename: M K
authors.initials: MK
authors.lastname: Parmar
authors.forename: I B
authors.initials: IB
authors.lastname: Vergote
authors.forename: A
authors.initials: A
authors.lastname: Gonzalez-Martin
authors.forename: D S
authors.initials: DS
authors.lastname: Alberts
authors.forename: M
authors.initials: M
authors.lastname: Plante
authors.forename: V
authors.initials: V
authors.lastname: Torri
authors.forename: J A
authors.initials: JA
authors.lastname: Ledermann
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D016190:Carboplatin; D002945:Cisplatin
keywords: IPD meta-analysis; recurrent ovarian cancer