title: Endpoints in adjuvant treatment trials: a systematic review of the literature in colon cancer and proposed definitions for future trials.
abstract: Disease-free survival is increasingly being used as the primary endpoint of most trials testing adjuvant treatments in cancer. Other frequently used endpoints include overall survival, recurrence-free survival, and time to recurrence. These endpoints are often defined differently in different trials in the same type of cancer, leading to a lack of comparability among trials. In this Commentary, we used adjuvant studies in colon cancer as a model to address this issue. In a systematic review of the literature, we identified 52 studies of adjuvant treatment in colon cancer published in 1997-2006 that used eight other endpoints in addition to overall survival. Both the definition of these endpoints and the starting point for measuring time to the events that constituted these endpoints varied widely. A panel of experts on clinical research on colorectal cancer then reached consensus on the definition of each endpoint. Disease-free survival--defined as the time from randomization to any event, irrespective of cause--was considered to be the most informative endpoint for assessing the effect of treatment and therefore the most relevant to clinical practice. The proposed guidelines may add to the quality and cross-comparability of future studies of adjuvant treatments for cancer.
authors.affiliation: Department of Medical Oncology, Radboud University Nijmegen Medical Center, PO Box 9101 6500 HB Nijmegen, The Netherlands. c.punt@onco.umcn.nl
authors.forename: Cornelis J A
authors.initials: CJ
authors.lastname: Punt
authors.forename: Marc
authors.initials: M
authors.lastname: Buyse
authors.forename: Claus-Henning
authors.initials: CH
authors.lastname: Köhne
authors.forename: Peter
authors.initials: P
authors.lastname: Hohenberger
authors.forename: Roberto
authors.initials: R
authors.lastname: Labianca
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Schmoll
authors.forename: Lars
authors.initials: L
authors.lastname: Påhlman
authors.forename: Alberto
authors.initials: A
authors.lastname: Sobrero
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Douillard
mesh_terms: D017024:Chemotherapy, Adjuvant / Q000379:methods*; D002986:Clinical Trials as Topic; D003110:Colonic Neoplasms / Q000628:therapy*; D018450:Disease Progression; D018572:Disease-Free Survival; D006801:Humans; D017063:Outcome Assessment, Health Care; D012107:Research Design; D015996:Survival Rate; D013997:Time Factors; D017211:Treatment Failure; D016896:Treatment Outcome