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Medline ® Abstract for Reference 18

of 'Adjuvant therapy for resected stage III (node-positive) colon cancer'

18
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Two or three year disease-free survival (DFS) as a primary end-point in stage III adjuvant colon cancer trials with fluoropyrimidines with or without oxaliplatin or irinotecan: data from 12,676 patients from MOSAIC, X-ACT, PETACC-3, C-06, C-07 and C89803.
AU
Sargent D, Shi Q, Yothers G, Van Cutsem E, Cassidy J, Saltz L, Wolmark N, Bot B, Grothey A, Buyse M, de Gramont A, Adjuvant Colon Cancer End-points (ACCENT) Group
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Eur J Cancer. 2011;47(7):990. Epub 2011 Jan 21.
 
BACKGROUND: The ACCENT group previously established disease-free survival (DFS) with 2 or 3 years median follow-up to predict 5 year overall survival (5 year OS) in stage II and III colon cancer. ACCENT further proposed (1) a stronger association between DFS and OS in stage III than II, and (2) 6 or 7 years necessary to demonstrate DFS/OS surrogacy in recent trials. The relationship between end-points in trials with oral fluoropyrimidines, oxaliplatin and irinotecan is unknown.
METHODS: Associations between the treatment effect hazard ratios (HRs) on 2 and 3 years DFS, and 5 and 6 years OS were examined in 6 phase III trials not included in prior analyses from 1997 to 2002. Individual data for 12,676 patients were analysed; two trials each tested oxaliplatin, irinotecan and oral treatment versus 5-FU/LV.
FINDINGS: Overall association between 2/3 year DFS and 5/6 year OS HRs was modest to poor (simple R²measures: 0.58-0.76, model-based R²: 0.17-0.49). In stage III patients, the association increased (model-based R²≥0.79). Observed treatment effects on 2 year DFS accurately 5/6 year OS effects overall and in stage III patients.
INTERPRETATION: In recent trials of cytotoxic chemotherapy, 2 or 3 years DFS HRs are highly predictive of 5 and 6 years OS HRs in stage III but not stage II patients. In all patients the DFS/OS association is stronger for 6 year OS, thus at least 6 year follow-up is recommended to assess OS benefit. These data support DFS as the primary end-point for stage III colon cancer trials testing cytotoxic agents.
AD
NCCTG, Mayo Clinic, Rochester, MN, USA. sargent.daniel@mayo.edu
PMID