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.
- Author:
Xun CAI
1
;
Peng XUE
;
Wei-feng SONG
;
Jiong HU
;
Hong-li GU
;
Hai-yan YANG
;
Li-wei WANG
Author Information
- Publication Type:Journal Article
- MeSH: Adenocarcinoma; blood; drug therapy; pathology; Adenocarcinoma, Mucinous; blood; drug therapy; pathology; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; adverse effects; therapeutic use; Bone Marrow Diseases; chemically induced; Colonic Neoplasms; blood; drug therapy; pathology; Diarrhea; chemically induced; Disease-Free Survival; Female; Fluorouracil; adverse effects; blood; pharmacokinetics; therapeutic use; Humans; Leucovorin; adverse effects; therapeutic use; Male; Middle Aged; Mucositis; chemically induced; Neoplasm Staging; Organoplatinum Compounds; adverse effects; therapeutic use; Random Allocation; Rectal Neoplasms; blood; drug therapy; pathology; Remission Induction; Survival Rate
- From: Chinese Journal of Oncology 2012;34(1):39-43
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo 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.
METHODSEighty-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.
RESULTSThe 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).
CONCLUSIONSThe 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.
