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Clinical Benefit of Therapeutic Drug Monitoring in Colorectal Cancer Patients Who Received Fluorouracil-Based Chemotherapy.

ABSTRACT: BACKGROUND The impact of therapeutic drug management (TDM) on reducing toxicity and improving efficacy in colorectal cancer (CRC) patients receiving fluorouracil-based chemotherapy is still unclear. MATERIAL AND METHODS A total of 207 patients (Study Group n=54, Historical Group n=153) with metastatic colorectal cancer were enrolled. All of them received 6 administrations of the 5-FU based regimens. Initial 5-FU dosing of all patients was calculated using body surface area (BSA). In the Study Group, individual exposure during each cycle was measured using a nanoparticle immunoassay, and the 5-FU blood concentration was calculated using the area under the curve (AUC). We adjusted the 5-FU infusion dose of the next cycle based on the AUC data of the previous cycle to achieve the target of 20-30 mg×h/L. RESULTS In the fourth cycle, patients in the target concentration range (AUC mean, 26.3 mg×h/L; Median, 28 mg×h/L; Range, 14-38 mg×h/L; CV, 22.4%) accounted for 46.8% of all patients, which were more than the ones in the first cycle (P<0.001). 5-FU TDM significantly reduced the toxicity of chemotherapy and improved its efficacy. The Study Group (30/289) showed a lower percentage of severe adverse events than that in the Historical Group (185/447) (P<0.001). The incidences of complete response and partial response in the Study Group were higher than those in the Historical Group (P=0.032). CONCLUSIONS TDM in colorectal cancer can reduce toxicity, improve efficacy and clinical outcome, and can be routinely used in 5-FU-based chemotherapy.

SUBMITTER: Zhou X

PROVIDER: S-EPMC8336255 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionBody surface area (BSA)-based dosing of 5-fluorouracil (5-FU) results in marked inter-individual variability in drug levels, whereas determination of plasma 5-FU concentration and area under the curve (AUC) is a more precise dosing method but has not been integrated into clinical routine. We conducted a multicenter, prospective study to study 5-FU AUC distributions and assess clinical factors predicting therapeutic dosing in patients receiving BSA-dosed 5-FU.MethodsBetween June 2017 and January 2018, a total of 434 patients receiving continuous, infusional BSA-dosed 5-FU from 37 sites in Germany were included. Plasma 5-FU concentration and AUC were measured in venous blood samples at steady state. The primary objective was to determine 5-FU AUC distributions in relation to the target range, which is defined as 20-30 mg × h/l. The second objective was to explore clinical parameters that correlate with achievement of 5-FU AUC target range.ResultsThe primary tumor was mainly located in the gastrointestinal tract (96.3%), with colorectal cancer being the most common (71.2%) tumor entity. 5-FU was administered as monotherapy (8.1%) or as part of FOLFOX (33.2%), FOLFIRI (26.3%), or other regimens (12.4%). Treatment setting was adjuvant (31.3%) or metastatic (64.5%). The median AUC was 16 mg × h/l. Only 20.3% of patients received 5-FU treatment within the target range, whereas the majority of patients (60.6%) were underdosed and 19.1% of patients were overdosed. In the univariate logistic regression, treatment setting was the only clinical parameter that significantly correlated with achievement of the target range. Patients treated in the metastatic setting had a 2.1 (95% confidence interval 1.186-3.776, P = 0.011) higher odds to reach the target range compared with patients treated in the adjuvant setting.ConclusionsThe majority of patients received suboptimal doses of 5-FU using BSA dosing. Therapeutic drug monitoring of 5-FU is an option for optimized individualized cancer therapy and should be integrated into the clinical practice.

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Clinical Benefit of Therapeutic Drug Monitoring in Colorectal Cancer Patients Who Received Fluorouracil-Based Chemotherapy.

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