A review of the bioanalytical methods for the quantitative determination of capecitabine and its metabolites in biological matrices

The bioanalysis of the oral anticancer drug capecitabine and its metabolites has been investigated extensively over the past years. This paper reviews methods for the bioanalysis of capecitabine and its metabolites. The focus of this review will be on sample pre-treatment, chromatography and detection. Furthermore, the choice of standards and analytical problems encountered during analysis of capecitabine and its metabolites in biological matrices will be discussed. The major challenges in the bioanalysis of capecitabine and its metabolites are the simultaneous extraction and analysis due to the differences in polarity of the analytes. Furthermore we evaluate currently described methods for the quantification of capecitabine and its metabolites. Future wishes and perspectives are stated that could serve as an inspiration for further development of assays for the quantification of capecitabine and its metabolites

A review of the bioanalytical methods for the quantitative determination of capecitabine and its metabolites in biological matrices

The bioanalysis of the oral anticancer drug capecitabine and its metabolites has been investigated extensively over the past years. This paper reviews methods for the bioanalysis of capecitabine and its metabolites. The focus of this review will be on sample pre-treatment, chromatography and detection. Furthermore, the choice of standards and analytical problems encountered during analysis of capecitabine and its metabolites in biological matrices will be discussed. The major challenges in the bioanalysis of capecitabine and its metabolites are the simultaneous extraction and analysis due to the differences in polarity of the analytes. Furthermore we evaluate currently described methods for the quantification of capecitabine and its metabolites. Future wishes and perspectives are stated that could serve as an inspiration for further development of assays for the quantification of capecitabine and its metabolites

Survival of Patients With Cancer With DPYD Variant Alleles and Dose-Individualized Fluoropyrimidine Therapy-A Matched-Pair Analysis

PURPOSE DPYD-guided fluoropyrimidine dosing improves patient safety in carriers of DPYD variant alleles. However, the impact on treatment outcome in these patients is largely unknown. Therefore, progression-free survival (PFS) and overall survival (OS) were compared between DPYD variant carriers treated with a reduced dose and DPYD wild-type controls receiving a full fluoropyrimidine dose in a retrospective matched-pair survival analysis. METHODS Data from a prospective multicenter study (ClinicalTrials.gov identifier: NCT02324452) in which DPYD variant carriers received a 25% (c.1236G&gt;A and c.2846A&gt;T) or 50% (DPYD*2A and c.1679T&gt;G) reduced dose and data from DPYD variant carriers treated with a similarly reduced dose of fluoropyrimidines identified during routine clinical care were obtained. Each DPYD variant carrier was matched to three DPYD wild-type controls treated with a standard dose. Survival analyses were performed using Kaplan-Meier estimates and Cox regression. RESULTS In total, 156 DPYD variant carriers and 775 DPYD wild-type controls were available for analysis. Sixty-one c.1236G&gt;A, 25 DPYD*2A, 13 c.2846A&gt;T, and—when pooled—93 DPYD variant carriers could each be matched to three unique DPYD wild-type controls. For pooled DPYD variant carriers, PFS (hazard ratio [HR], 1.23; 95% CI, 1.00 to 1.51; P 5 .053) and OS (HR, 0.95; 95% CI, 0.75 to 1.51; P 5 .698) were not negatively affected by DPYD-guided dose individualization. In the subgroup analyses, a shorter PFS (HR, 1.43; 95% CI, 1.10 to 1.86; P 5 .007) was found in c.1236G&gt;A variant carriers, whereas no differences were found for DPYD*2A and c.2846A&gt;T carriers. CONCLUSION In this exploratory analysis, DPYD-guided fluoropyrimidine dosing does not negatively affect PFS and OS in pooled DPYD variant carriers. Close monitoring with early dose modifications based on toxicity is recommended, especially for c.1236G&gt;A carriers receiving a reduced starting dose.</p

Survival of Patients With Cancer With DPYD Variant Alleles and Dose-Individualized Fluoropyrimidine Therapy-A Matched-Pair Analysis

PURPOSE: -guided fluoropyrimidine dosing improves patient safety in carriers of variant alleles. However, the impact on treatment outcome in these patients is largely unknown. Therefore, progression-free survival (PFS) and overall survival (OS) were compared between variant carriers treated with a reduced dose and wild-type controls receiving a full fluoropyrimidine dose in a retrospective matched-pair survival analysis. METHODS: Data from a prospective multicenter study (ClinicalTrials.gov identifier: NCT02324452) in which variant carriers received a 25% (c.1236G&gt;A and c.2846A&gt;T) or 50% ( *2A and c.1679T&gt;G) reduced dose and data from variant carriers treated with a similarly reduced dose of fluoropyrimidines identified during routine clinical care were obtained. Each variant carrier was matched to three wild-type controls treated with a standard dose. Survival analyses were performed using Kaplan-Meier estimates and Cox regression. RESULTS: In total, 156 variant carriers and 775 wild-type controls were available for analysis. Sixty-one c.1236G&gt;A, 25 *2A, 13 c.2846A&gt;T, and-when pooled-93 variant carriers could each be matched to three unique wild-type controls. For pooled variant carriers, PFS (hazard ratio [HR], 1.23; 95% CI, 1.00 to 1.51; = .053) and OS (HR, 0.95; 95% CI, 0.75 to 1.51; = .698) were not negatively affected by -guided dose individualization. In the subgroup analyses, a shorter PFS (HR, 1.43; 95% CI, 1.10 to 1.86; = .007) was found in c.1236G&gt;A variant carriers, whereas no differences were found for *2A and c.2846A&gt;T carriers. CONCLUSION: In this exploratory analysis, -guided fluoropyrimidine dosing does not negatively affect PFS and OS in pooled variant carriers. Close monitoring with early dose modifications based on toxicity is recommended, especially for c.1236G&gt;A carriers receiving a reduced starting dose