Impact of relative dose intensity on the outcome of metastatic colorectal cancer.

Abstract

508 Background: Relative dose intensity (RDI) is the ratio of delivered dose intensity of chemotherapy to standard dose intensity. There is established evidence supporting the significance of RDI in patients with various cancer, however data in patients with metastatic colorectal cancer (mCRC) are limited. In this study, we evaluate the significance of RDI of irinotecan and oxaliplatin-based chemotherapy on the outcome of mCRC. Methods: A retrospective analysis of mCRC patients entered into two prospective clinical trials, testing FOLFIRI (CCOG-0502) and mFOLFOX6 (CCOG-0704), was performed. RDI was calculated as the delivered dose intensity divided by standard dose intensity calculated for each regimen and compared to objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS). Results: The median RDI of irinotecan in FOLFIRI and oxaliplatin in mFOLFOX6 were 80% and 79%. ORRs In higher RDI (>median) group and lower RDI (<median) group were 64.7% and 5.9% of irinotecan (p=0.001), and 46.7% and 33.3% of oxaliplatin (p=0.456). DCRs in higher and lower group were 100% and 41.2% in FOLFIRI (p=0.003), and 100 and 73.3% in mFOLFOX6 (p=0.032). PFS in higher and lower group were 9.9 and 5.6 months in FOLFIRI (p=0.002), and 8.5 and 6.2 months in mFOLFOX6 (p=0.064). Conclusions: RDI of key cytotoxic agents is a significant predictor of disease control in patients with mCRC, especially in irinotecan-based regimen. Dose reductions and treatment delays could be minimized to achieve an RDI of at least 80%.