Maintaining the optimal dose of 5-FU is associated with increased efficacy

Target AUC range of 20 to 30 mg•h/L supports maximized efficacy without increasing toxicity.

  • Toxicity is more closely related to AUC of more than 30 mg•h/L (3000 μg/L) than to the dose of 5-FU2
  • A strong correlation was also shown between 5-FU plasma concentrations greater than 20 mg•h/L (2500 μg/L) and a response of the tumor to treatment2
  • Patients with 5-FU plasma levels lower than 20 mg•h/L (2500 μg/L) were dosed subtherapeutically and had a decreased rate of response3
Suboptimal dosing
  1. Gamelin E, Boisdron-Celle M, Guerin-Meyer V, et al. Correlation between uracil and dihydrouracil plasma ratio, Fluorouracil(5-FU) pharmacokinetic parameters, and tolerance in patients with advanced colorectal cancer: a potential interest for predicting 5-FU toxicity and determining optimal 5-FU dosage. J Clin Oncol. 1999;17:1105-1110.
  2. Gamelin EC, Danquechin-Dorval EM, Dumesnil YF, et al. Relationship between 5-Fluorouracil (5-FU) dose intensity and therapeutic response in patients with advanced colorectal cancer receiving infusional therapy containing 5-FU. Cancer. 1996;77:441-451.
  3. Gamelin E, Delva R, Jacob J, et al. Individual Fluorouracil dose adjustment based on pharmacokinetic follow-up compared with conventional dosage: results of a multicenter randomized trial of patients with metastatic colorectal cancer. J Clin Oncol. 2008;26:2099-2105.
  4. Ychou M, Duffour J, Kramar A, et al. Individual 5-FU dose adaptation in metastatic colorectal cancer: results of a phase II study using a bimonthly pharmacokinetically intensified LV5FU2 regimen. Cancer Chemother Pharmacol. 2003;52:282-290.