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Eur J Cancer. 2011 May;47(7):990-6. doi: 10.1016/j.ejca.2010.12.015. Epub 2011 Jan 21.

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.

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NCCTG, Mayo Clinic, Rochester, MN, USA.



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.


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.


Overall association between 2/3 year DFS and 5/6 year OS HRs was modest to poor (simple R² measures: 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.


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.

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