Authors' recommendations: Prior evidence supports the wide variability of 5‑FU plasma levels when patients are placed on a fixed-dose regimen. Evidence from one randomized, controlled trial in patients withadvanced colorectal cancer shows that measuring and adjusting 5‑FU to a target systemic exposure (AUC) results in a Gaussian distribution of 5‑FU administered doses, a large proportion of which are higher than a conventional fixed dose. Such uniform exposure resulted in improved clinical response and reduced toxicity. Improved tumor response was also consistently seen in previously published single-arm trials. However, the toxicity in terms of grade 3 to 4 diarrhea was higher in the control arm than seen in representative arms of other clinical trials enrolling comparable patient populations, suggesting a larger benefit in this trial than might be seen in actual practice. This trial also used a single-agent 5‑FU/leucovorin delivery regimen not commonly used in clinical practice, which may explain the increased toxicity in the control arm. As a result, and because changing the 5‑FU administration schedule and adding other antineoplastic drugs such as oxaliplatin that are part of currently used treatment regimens have been shown to affect 5‑FU clearance, the generalizability of the trial results are severely limited.A second randomized, controlled trial in patients with locally advanced head and neck cancer used a different method of dose adjustment, resulting in several dosing errors andthe authors' decision to remove these patients from the analysis, rather than conduct an intention-to-treat analysis that would reflect the "real world" results of the dose adjustmentmethod. Of the "evaluable" patients, those in the adjusted-dose arm received significantly lower 5‑FU doses on average than the fixeddose arm and had less toxicity, but no improvement in clinical response. The induction therapy regimen used 2 drugs, not the current standard of 3 and, therefore, these results are also limited in generalizability to current clinical practice.Given the limitations of the existing evidence, the evidence is insufficient to draw conclusions about the impact of 5‑FU exposure measurement and AUC-targeted dose adjustment on outcomes of patients administered contemporary chemotherapy regimens for colorectal or head and neck cancer.

Project Status: Completed

Year Published: 2009

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: United States

Organisation Name: BlueCross BlueShield Association

Contact Address: BlueCross BlueShield Association, Technology Evaluation Center, 225 North Michigan Ave, Chicago, Illinois, USA. Tel: 888 832 4321

Contact Name: tec@bcbsa.com

Contact Email: tec@bcbsa.com

Copyright: <p>BlueCross BlueShield Association (BCBS)</p>