Early versus delayed treatment of relapsed ovarian cancer (MRC OV05/EORTC 55955): a randomised trial.
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.
Rustin
Gordon J S
GJ
Mount Vernon Cancer Centre, Northwood, UK.
van der Burg
Maria E L
ME
Griffin
Clare L
CL
Guthrie
David
D
Lamont
Alan
A
Jayson
Gordon C
GC
Kristensen
Gunnar
G
Mediola
César
C
Coens
Corneel
C
Qian
Wendi
W
Parmar
Mahesh K B
MK
Swart
Ann Marie
AM
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
D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D017671:Platinum Compounds