X-ACT: an important step on an unfinished journey.

L et al Detection and HER2 expression of circulating tumor cells: prospective monitoring in breast cancer patients treated in the neoadjuvant GeparQuattro trial. Campion M et al CTCs and HER2-positive CTCs detection by CellSearch® in non-metastatic breast cancer: an international ring study to assess inter-reader variability. et al The therapeutic effect of anti-HER2/neu antibody depends on both innate and adaptive immunity. The adjuvant chemotherapy treatment of stage III colorectal cancer has saved thousands of lives over the last 20 years since the first evidence of the benefit of 5FU and levamisole was reported [1]. The benefit from 5FU based regimens is risk related. Collated data, analysed by the ACCENT investigators from eight years of follow up for 20,898 patients in 18 randomised trials of 5FU based chemotherapy versus control, showed that the absolute improvement in overall survival was 10% for patients with stage III colorectal cancer [2]. Since those initial studies and the refinement of them to the standard of care in the mid to late 1990s of 6 months therapy with bolus 5FU and leucovorin (5FU/LV) regimens, there have been only two practice changing sets of evidence in this field of practice. The first was the introduction of an oral alternative to the bolus 5FU/LV regimens, using either capecitabine or Uftoral [3,4] and the second the introduction of oxaliplatin [5-7]. In a recent edition of Annals the long term outcomes of the X-ACT trial were reported, which confirm the non-inferiority of the oral 5FU prodrug, capecitabine, in comparison with one of the previous international standards, the Mayo clinic bolus 5FU/LV regimen in the adjuvant treatment of stage III colorectal cancer [8]. The X-ACT trial recruited about 2000 patients from many countries internationally, between 1998 and 2001 and has now been extensively reported. The characteristics of the patients in the study were well balanced, with if anything slightly worse prognostic factors in the capecitabine group, though with no statistically significant differences. Elevated CEA was present in 8.6% of the capecitabine group compared to 7% of control; N2 disease (four or more involved nodes) was present in 30.8% versus 29.4% respectively. The primary endpoint of the X-ACT trial was 3 year disease free survival (DFS) and the statistical plan required 632 events to exclude a non-inferiority margin of 1.25 with a type 1 error of 2.5%. At the time of original publication, 728 DFS events had occurred and 427 patients had …