[Role of pharmacokinetic monitoring of serum fluorouracil concentration in patients with local advanced and metastatic colorectal cancer and further improving efficacy of fluorouracil-based chemotherapy]

Zhonghua Zhong Liu Za Zhi. 2012 Jan;34(1):39-43.
[Article in Chinese]

Abstract

Objective: To investigate the relationship between serum concentration of fluorouracil and therapeutic efficacy as well as adverse reactions in patients with unresectable locally advanced or measurable metastatic colorectal cancer, and to analyze its role in further improving therapeutic efficacy and reducing adverse reactions of fluorouracil-based chemotherapy.

Methods: Eighty-six patients were randomly assigned into three groups according to the average plasma concentration of fluorouracil after three cycles of chemotherapy with the initial regimen of two weeks FOLFOX-4 (oxaliplatin + leucovorin + fluorouracil) or FOLFIRI (irinotecan + leucovorin + fluorouracil): group 1 (plasma concentration of fluorouracil < 25 ng/ml), group 2 (25 - 35 ng/ml) and group 3 (> 35 ng/ml). The blood samples were taken at 12 h after continuous infusion of fluorouracil in each cycle and the plasma concentration of fluorouracil was detected by high performance liquid chromatography (HPLC) (about 5 am ± 1 h). The relationship between the drug plasma concentration, therapeutic efficacy and adverse reactions in different fluorouracil plasma concentration arms was analyzed retrospectively.

Results: The average plasma concentrations of fluorouracil of the three groups were (23.48 ± 1.95) ng/ml, (31.47 ± 2.33) ng/ml and (39.89 ± 3.87) ng/ml, respectively (P < 0.01). As for therapeutic efficacy, the median OS of the groups 2 and 3 were 18.0 and 17.5 months, significantly higher than that in the group 1 (13.0 months, P < 0.01). The PFS were 4.5, 7.5 and 8.0 months, respectively (P < 0.01). In terms of adverse reactions, the incidences of bone marrow suppression, mucositis and diarrhea in the group 3 were significantly higher than that in the first two groups (P = 0.02, P = 0.04 and P = 0.02).

Conclusions: The patients with local advanced and metastatic colorectal cancer, receiving fluorouracil-based chemotherapy, and with an average plasma concentration of fluorouracil between 25 - 35 mg/L have a better prognosis, and lower incidence of adverse reactions such as bone marrow suppression, mucositis and diarrhea.

Publication types

  • English Abstract

MeSH terms

  • Adenocarcinoma* / blood
  • Adenocarcinoma* / drug therapy
  • Adenocarcinoma* / pathology
  • Adenocarcinoma, Mucinous / blood
  • Adenocarcinoma, Mucinous / drug therapy
  • Adenocarcinoma, Mucinous / pathology
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bone Marrow Diseases / chemically induced
  • Colonic Neoplasms* / blood
  • Colonic Neoplasms* / drug therapy
  • Colonic Neoplasms* / pathology
  • Diarrhea / chemically induced
  • Disease-Free Survival
  • Female
  • Fluorouracil / adverse effects
  • Fluorouracil / blood
  • Fluorouracil / pharmacokinetics*
  • Fluorouracil / therapeutic use
  • Humans
  • Leucovorin / adverse effects
  • Leucovorin / therapeutic use
  • Male
  • Middle Aged
  • Mucositis / chemically induced
  • Neoplasm Staging
  • Organoplatinum Compounds / adverse effects
  • Organoplatinum Compounds / therapeutic use
  • Random Allocation
  • Rectal Neoplasms* / blood
  • Rectal Neoplasms* / drug therapy
  • Rectal Neoplasms* / pathology
  • Remission Induction
  • Survival Rate

Substances

  • Organoplatinum Compounds
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol