Individual 5-Fluorouracil Dose Adjustment via Pharmacokinetic Monitoring Versus Conventional Body-Area-Surface Method: A Meta-Analysis

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Abstract

Background:

Recent studies suggest that 5-fluorouracil (5-FU) dosing by use of pharmacokinetic (PK) parameters is superior to the traditional body surface area (BSA) method in colorectal cancer therapy. The purpose of this study was to compare the estimated efficacy and toxicity of the use of PK-guided versus BSA-based dose adjustment of 5-FU in advanced cancers.

Methods:

The authors searched from electronic databases (up to September, 2014) and abstracts presented at the American Society of Clinical Oncology held between 2000 and 2014 for studies comparing the response rate and toxicity in 5-FU–based chemotherapy.

Results:

Five eligible articles with 654 patients were included in double-arms and contained colorectal cancer, and head and neck cancer. PK-monitored 5-FU therapy was associated with significant improvement in overall response rate (odds ratio = 2.04, 95% confidence interval, 1.41–2.95, Z = 3.78, P = 0.0002) compared with the traditional BSA method. There was no evidence of improved tolerability: grade 3 to 4 diarrhea, neutropenia, and hand-foot syndrome were found not to be significantly different except that mucositis was less prominent for PK-monitored 5-FU therapy (odds ratio = 0.16, 95% confidence interval, 0.04–0.63, Z = 2.62, P = 0.009).

Conclusions:

In comparison with conventional BSA method, PK-based 5-FU dosage confirmed a superior overall response rate and improved toxicities irrespective of significant difference, the results of which indicated that PK- monitored 5-FU dosage has the potential to be performed in colorectal cancer personalized therapy. More high-quality and multicenter randomized controlled trails should be carried out to provide more information for comparing the response and toxicity of these 2 dose adjustment methods.

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