A Community-Based Multicenter Trial of Pharmacokinetically Guided 5-Fluorouracil Dosing for Personalized Colorectal Cancer Therapy

Background. Pharmacokinetically guided (PK-guided) versus body surface area-based 5-fluorouracil (5-FU) dosing results in higher response rates and better tolerability. A paucity of data exists on PK-guided 5-FU dosing in the community setting. Patients and Methods. Seventy colorectal cancer patients, from1academicand5communitycancercenters,receivedthe mFOLFOX6 regimen (5-FU 2,400 mg/m 2 over 46 hours every 2 weeks) with or without bevacizumab at cycle 1. The 5-FU continuous-infusion dose was adjusted for cycles 2–4 using a PK-guided algorithm to achieve a literature-based target area under the concentration-time curve (AUC). The primary objective was to demonstrate that PK-guided 5-FU dosing improvesthe abilitytoachievea targetAUCwithin fourcycles of therapy. The secondary objective was to demonstrate reduced incidence of 5-FU-related toxicities. Results. At cycles 1 and 4, 27.7% and 46.8% of patients