In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 4_suppl ( 2017-02-01), p. 650-650
Abstract:
650 Background: Studies have demonstrated that body surface area (BSA)-based dosing of chemotherapy drugs leads to significant individual exposure variability with a substantial risk of under- or overdosing. This study was initiated to validate use of TDM to personalize 5-FU dosing in mCRC patients treated in routine clinical practice. Methods: 75 mCRC patients from 8 German medical centers received up to 6 administrations of infusional 5-FU according to either the AIO (n = 16), FOLFOX6 (n = 26) or FUFOX (n = 33) regimen. Initial infusional 5-FU dosing for all patients was based on BSA. Individual 5-FU exposure (AUC) was measured by an immunoassay using a blood sample drawn during each infusion. To achieve target AUC of 20 to 30 mg•h/L, subsequent infusional 5-FU doses were adjusted according to the previous cycle 5-FU AUC. Tumor markers CEA and CA19-9 were also measured before, during and after treatment. Primary objective was to confirm TDM of infusional 5-FU resulted in an increased proportion of patients in the target AUC range at the 4 th versus the 1 st administration. Secondary objective was to determine whether 5-FU TDM reduced treatment-related toxicities compared to historical data. Results: Average 5-FU AUC at 1 st administration was 18 + 6 mg•h/L, with 64%, 33% and 3% of the patients below, within or above target AUC range, respectively. By the 4 th administration average 5-FU AUC was 25 + 7 mg•h/L (p 〈 0.001), with 54% patients within the target 5-FU AUC range (p = 0.0294). Compared to baseline levels, CEA and CA19-9 remained stable or decreased at the end of treatment in 82% and 84% of the patients, respectively. 5-FU-related grade 3-4 diarrhea (4.6%), nausea (3.4%), fatigue (0.0%) and mucositis (0.2%) were reduced compared to historical data inspite of 55% of patients having their doses increased. Conclusions: Personalization of 5-FU dosing via TDM in routine clinical practice resulted in significantly improved 5-FU exposure and suggested lower 5-FU-related toxicities. Clinical trial information: 2011-003553-26.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2017.35.4_suppl.650
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2017
detail.hit.zdb_id:
2005181-5
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