title: Early versus delayed treatment of relapsed ovarian cancer (MRC OV05/EORTC 55955): a randomised trial.
abstract: BACKGROUND
  Serum CA125 concentration often rises several months before clinical or symptomatic relapse in women with ovarian cancer. In the MRC OV05/EORTC 55955 collaborative trial, we aimed to establish the benefits of early treatment on the basis of increased CA125 concentrations compared with delayed treatment on the basis of clinical recurrence.
  
  
  METHODS
  Women with ovarian cancer in complete remission after first-line platinum-based chemotherapy and a normal CA125 concentration were registered for this randomised controlled trial. Clinical examination and CA125 measurement were done every 3 months. Patients and investigators were masked to CA125 results, which were monitored by coordinating centres. If CA125 concentration exceeded twice the upper limit of normal, patients were randomly assigned (1:1) by minimisation to early or delayed chemotherapy. Patients and clinical sites were informed of allocation to early treatment, and treatment was started as soon as possible within 28 days of the increased CA125 measurement. Patients assigned to delayed treatment continued masked CA125 measurements, with treatment commencing at clinical or symptomatic relapse. All patients were treated according to standard local practice. The primary outcome was overall survival. Analysis was by intention to treat. This study is registered, ISRCTN87786644.
  
  
  RESULTS
  1442 patients were registered for the trial, of whom 529 were randomly assigned to treatment groups and were included in our analysis (265 early, 264 delayed). With a median follow-up of 56·9 months (IQR 37·4-81·8) from randomisation and 370 deaths (186 early, 184 delayed), there was no evidence of a difference in overall survival between early and delayed treatment (HR 0·98, 95% CI 0·80-1·20, p=0·85). Median survival from randomisation was 25·7 months (95% CI 23·0-27·9) for patients on early treatment and 27·1 months (22·8-30·9) for those on delayed treatment.
  
  
  CONCLUSIONS
  Our findings showed no evidence of a survival benefit with early treatment of relapse on the basis of a raised CA125 concentration alone, and therefore the value of routine measurement of CA125 in the follow-up of patients with ovarian cancer who attain a complete response after first-line treatment is not proven.
  
  
  BACKGROUND
  UK Medical Research Council and the European Organisation for Research and Treatment of Cancer.
authors.affiliation: Mount Vernon Cancer Centre, Northwood, UK.
authors.forename: Gordon J S
authors.initials: GJ
authors.lastname: Rustin
authors.forename: Maria E L
authors.initials: ME
authors.lastname: van der Burg
authors.forename: Clare L
authors.initials: CL
authors.lastname: Griffin
authors.forename: David
authors.initials: D
authors.lastname: Guthrie
authors.forename: Alan
authors.initials: A
authors.lastname: Lamont
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Jayson
authors.forename: Gunnar
authors.initials: G
authors.lastname: Kristensen
authors.forename: César
authors.initials: C
authors.lastname: Mediola
authors.forename: Corneel
authors.initials: C
authors.lastname: Coens
authors.forename: Wendi
authors.initials: W
authors.lastname: Qian
authors.forename: Mahesh K B
authors.initials: MK
authors.lastname: Parmar
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Swart
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood*; D002277:Carcinoma / Q000175:diagnosis* / Q000188:drug therapy* / Q000276:immunology; D004334:Drug Administration Schedule; D055088:Early Detection of Cancer; D005060:Europe; D019317:Evidence-Based Medicine; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000276:immunology; D017671:Platinum Compounds / Q000008:administration & dosage; D011788:Quality of Life; D012426:Russia; D013019:South Africa; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D017671:Platinum Compounds