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Clin Colorectal Cancer. 2016 Dec;15(4):381-388. doi: 10.1016/j.clcc.2016.04.001. Epub 2016 May 7.

Prospective, Multicenter Study of 5-Fluorouracil Therapeutic Drug Monitoring in Metastatic Colorectal Cancer Treated in Routine Clinical Practice.

Author information

1
Department of Hematology and Medical Oncology, Paracelsus Medical University, Nuremberg, Germany. Electronic address: Martin.Wilhelm@klinikum-nuernberg.de.
2
Outpatient Clinic, Leer, Germany.
3
Saladax Biomedical Inc., Bethlehem, PA.
4
Outpatient Clinic, Lueneburg, Germany.
5
Institute for Clinical Chemistry and Pharmacology, University of Bonn, Bonn, Germany.
6
Central Laboratory, Paracelsus Medical University, Nuremberg, Germany.
7
University Clinic of Wuerzburg, Wuerzburg, Germany.
8
Hemato-Oncologic Clinic, Munich, Germany.
9
Oncological Center, Munich, Germany.
10
Clinic Barmherzige Brueder, Regensburg, Germany.
11
Department of Hematology and Medical Oncology, Paracelsus Medical University, Nuremberg, Germany.
12
CESAR Central European Society for Anticancer Drug Research-EWIV, Vienna, Austria.
13
Pharmaceutical Institute, University Bonn, Bonn, Germany.

Abstract

BACKGROUND:

Studies have demonstrated that body surface area-based dosing of chemotherapy drugs leads to significant individual exposure variability, with a substantial risk of under- or overdosing. The present study was initiated to validate the use of therapeutic drug management (TDM) to personalize 5-fluorouracil (5-FU) dosing in patients with metastatic colorectal cancer treated in routine clinical practice.

PATIENTS AND METHODS:

A total of 75 patients with metastatic colorectal cancer from 8 German medical centers received ≤ 6 administrations of infusional 5-FU according to the AIO (folinate, 5-FU; n = 16), FOLFOX6 (leucovorin calcium [folinic acid], 5-FU, and oxaliplatin; n = 26), or FUFOX (oxaliplatin plus 5-FU/folinic acid; n = 33) regimen. Initial infusional 5-FU dosing for all patients was determined by the BSA. Individual 5-FU exposure (area under the curve [AUC]) was measured using an immunoassay of a blood sample taken during each infusion. To achieve a target AUC of 20 to 30 mg × h/L, subsequent infusional 5-FU doses were adjusted according to the previous cycle's 5-FU AUC. The primary objective was to confirm that TDM of infusional 5-FU resulted in an increased proportion of patients in the target AUC range at the fourth versus the first administration. The secondary objective was to determine whether 5-FU TDM reduced the treatment-related toxicities compared with the historical data.

RESULTS:

The average 5-FU AUC at the first administration was 18 ± 6 mg × h/L, with 64%, 33%, and 3% of the patients below, within, or above the target AUC range, respectively. By the fourth administration, the average 5-FU AUC was 25 ± 7 mg × h/L (P < .001), with 54% of patients within the target 5-FU AUC range (P = .0294). The incidence of 5-FU-related grade 3 and 4 diarrhea (4.6%), nausea (3.4%), fatigue (0.0%), and mucositis (0.2%) was reduced compared with the historical data, despite 55% of the patients receiving increased doses.

CONCLUSION:

Personalization of 5-FU dosing using TDM in routine clinical practice resulted in significantly improved 5-FU exposure and suggested a lower incidence of 5-FU-related toxicities.

KEYWORDS:

5-FU; Colorectal cancer; Dosing; Therapeutic drug monitoring

PMID:
27256667
DOI:
10.1016/j.clcc.2016.04.001
[Indexed for MEDLINE]

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