Impact of relative dose intensity and G-CSF use in the adjuvant treatment of resected colon cancer.

Abstract

752 Background: The benefits of adjuvant chemotherapy in stage III colon cancer (CC) are well established. However, the consequences of dose delays and modifications are not well established. Relative dose intensity (RDI) and dose scheduling have been shown to have prognostic significance in a number of cancers. We examine the effect of RDI, dose intensity (DI) and dose delays on disease free survival (DFS) and overall survival (OS) in stage III CC. Furthermore, we investigate the role of G-CSF in CC and its role in preserving RDI, and its effect on outcomes. Methods: A retrospective review was conducted for patients with stage III CC seen at a Canadian academic cancer center between 2006 and 2011. Patients who received at least three cycles of FOLFOX or at least two cycles capecitabine were included in the analysis. The RDI and DI were calculated and examined for correlation with DFS and OS. The influence of G-CSF on RDI and DI was also investigated. Results: FOLFOX was used more commonly than capecitabine, 64% vs. 36%. Within the FOLFOX regimen median RDI for oxaliplatin was 76.3%, and 83.5% for 5-FU. Median capecitabine RDI was 73.8%. Median DI were similar at 75.4%, 86.5%, and 69.1%, respectively. 60% of patients receiving FOLFOX got over 80% of their intended dose, while only 29% of patients receiving capecitabine achieved this DI. 3-year DFS was higher when RDI or DI was > 80%, compared to ≤ 80%, for each chemotherapeutic, however the differences did not reach significance. 3-year OS trended towards being higher in patients with an RDI and DI > than 80%, however there were limited events in these groups. Over half of patients on FOLFOX experienced a dose delay, 56.9%, most of whom then received G-CSF, 64.9%. Patients who received G-CSF had a higher DI than those who did not, 74.9% and 87.4% versus 66.5% and 76.8%, for the oxaliplatin and 5-FU components, respectively. 3-year DFS and OS was higher in patients who received G-CSF versus those who did not, 78.3% and 97.5% vs. 69.8% and 91.5%, respectively. Conclusions: In patients with stage III colon cancer an RDI or DI is associated with improved 3-year DFS and OS, although the difference did not reach significance in our review. G-CSF as secondary prophylaxis improves RDI, DI, DFS and OS.