A prospective, multi-center study of individualized, pharmacokinetically (PK)-guided dosing of 5-fluorouracil (5-FU) in metastatic colorectal cancer (mCRC) patients treated with weekly or biweekly 5-FU/oxaliplatin containing regimens.

3542 Background: Numerousstudies have demonstrated that body surface area (BSA)-based dosing leads to under- and overexposure in a large number of patients. PK-guided dosing of 5-FU can optimize 5-FU exposure resulting in higher overall dose intensity with reduced toxicities and improved outcomes. This study was initiated to validate use of PK-guided 5-FU dosing for mCRC patients in clinical practice. Methods: 75 mCRC patients from 8 academic and/or community-based medical centers located throughout Germany received up to 6 cycles of infusional 5-FU according to either the AIO (n = 16), FOLFOX6 (n = 26) or FUFOX (n = 33) regimen. Initial dosing of infusional 5-FU for all patients was based on BSA and subsequent doses were adjusted according to the previous cycle 5-FU area under the concentration-time curve (AUC) to target an AUC of 20 to 30 mg•h/L. Primary objective was to confirm that PK-guided dosing of 5-FU leads to an increased proportion of patients in the target AUC range at cycle 4 versus cycle 1. ...