5% CIs. An additional exploratory analysis of OS was performed to control for any possible crossover effects of FOLFOX in patients who received XELOX as their first-line regimen. In this analysis, patients in the XELOX arms who received http://www.selleckchem.com/products/ABT-888.html FOLFOX4 or similar regimen as second-line therapy were censored. Results Patient population Between July 2003 and May 2004, 634 patients were randomised in the two-arm portion of the study. Between February 2004 and February 2005, a further 1400 patients were randomised in the 2 �� 2 factorial part of the study. Overall, 2034 patients made up the ITT population (Figure 1). The baseline demographic and clinical characteristics were well balanced between treatment arms (Table 1). Figure 1 The CONSORT flowchart.

Table 1 Baseline patient characteristics (ITT population) Treatment exposure and second-line therapy The median dose intensities (ratio of dose received to dose planned) of 5-FU, capecitabine, oxaliplatin and bevacizumab were 0.89 in all treatment arms. The median number of cycles administered was 11 (range 1�C24) in the FOLFOX4/FOLFOX4-placebo group, 12 (range 1�C25) in the FOLFOX4-bevacizumab group, 7 (range 1�C18) in the XELOX/XELOX-placebo group and 8 (range 1�C17) in the XELOX-bevacizumab group. There were no major imbalances between the treatment groups with respect to the use of second-line therapy: XELOX-containing arms (65%) and FOLFOX4-containing arms (70%). The agents most commonly used were: irinotecan (56% with FOLFOX4 vs 53% with XELOX); 5-FU (41 vs 34%); capecitabine (19 vs 14%); cetuximab (20 vs 18%); and bevacizumab (10 vs 10%).

Overall survival The OS data as at 31 July 2008 in the ITT population are shown in Table 2. The corresponding Kaplan�CMeier curves for OS are shown in Figure 2. Figure 2 Overall survival for FOLFOX4/FOLFOX4-placebo/FOLFOX4-bevacizumab vs XELOX/XELOX-placebo/XELOX-bevacizumab (A), FOLFOX4/FOLFOX4-placebo vs XELOX/XELOX-placebo (B), FOLFOX4-bevacizumab vs XELOX-bevacizumab (C) and FOLFOX4 vs XELOX (D) (ITT population). Table 2 Overall survival by treatment subgroup (ITT population) For the whole NO16966 study population, median OS was 19.8 months in the pooled XELOX/XELOX-placebo/XELOX-bevacizumab arms vs 19.5 months in the pooled FOLFOX4/FOLFOX4-placebo/FOLFOX4-bevacizumab arms, with a corresponding HR of 0.95 (97.5% CI 0.85�C1.06). In the pooled XELOX/XELOX-placebo arms, median OS was 19.

0 vs 18.9 months in the pooled FOLFOX4/FOLFOX4-placebo arms, with a corresponding HR of 0.95 (97.5% CI 0.83�C1.09). In the XELOX-bevacizumab arm, median OS was 21.6 vs 21.0 Batimastat months in the FOLFOX4-bevacizumab arm, with a corresponding HR of 0.95 (97.5% CI 0.78�C1.15). In the XELOX arm, median OS was 18.8 vs 17.7 months in the FOLFOX4 arm, with a corresponding HR of 0.87 (97.5% CI 0.72�C1.05).