Focusing specifically on patients with colorectal cancer, what clinical evidence supports the value of pharmacokinetically (PK)-guided dosing of infusional 5-FU in this patient population?
Dr. Erick Gamelin and his colleagues recently published an important study in the Journal of Clinical Oncology. The purpose of the study was to assess the value of a PK-guided infusional 5-FU dose adjustment in controlling toxicity and improving efficacy in patients with metastatic colorectal cancer.206 This group conducted a phase 3, multicenter study that compared body surface area (BSA)-based dosing of infusional 5-FU plus leucovorin with PK-guided dose adjustment. In this study, each arm consisted of 104 patients who were treated with 5-FU (1500 mg/m2/week 8-hour continuous infusion with 400 mg/m2 of leucovorin). One arm used conventional BSA-based dosing. In the other arm, patients were dosed according to BSA in the first cycle with subsequent doses adjusted to a target level of 20-24 mg•h/L, based on drug levels determined by HPLC-based monitoring in the previous cycle.206 In terms of clinical efficacy, patients who received infusional 5-FU with PK-guided dosing had an objective
