Capecitabine is effective in treating colorectal cancer and is increasingly being investigated for use in preoperative chemoradiation of rectal cancer. Since capecitabine and its metabolites have a plasma half-life of 0.5-1 hour, the relative timing of capecitabine and radiotherapy may affect clinical outcomes. We retrospectively investigated whether the timing of radiotherapy affects rates of acute toxicity, pathologic response, and relapse in rectal cancer patients receiving capecitabine.

Between June 2001 and July 2004, 111 rectal cancer patients were treated with preoperative radiotherapy and concurrent capecitabine given twice daily, in the early morning and at night. Of these, 44 received at least 70% of their radiation treatments before 12 PM (AM group), and 47 received at least 70% of their radiation treatments after 12 PM (PM group).

There were no significant differences between the AM vs. PM groups in rates of grade >/= 2 acute gastrointestinal toxicity (61% vs. 47%) or skin toxicity (23% vs. 26%) or grades >/= 1 hand-foot syndrome (27% vs. 15%). Although the PM group had numerically higher rates of pathologic complete response (28% vs. 16%) and tumor downstaging (57% vs. 39%), differences in these outcomes and in sphincter preservation were not significant. Rates of 2-year local control, distant control, and disease-free survival were nearly identical in the two groups.

No significant differences were seen in the rates of acute toxicity, pathologic response, and relapse between patients in the AM and PM groups. The timing of radiotherapy does not appear to be critical in patients with rectal cancer receiving concurrent capecitabine.