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Prevention of Capecitabine Toxicity Using a 5-FU Test Dose

[ Vol. 4 , Issue. 2 ]

Author(s):

Teresa Di Desidero, Cecilia Barbara, Paola Orlandi, Anna Fioravanti, Fotios Loupakis, Chiara Cremolini, Giacomo Allegrini, Antonello Di Paolo, Alfredo Falcone, Romano Danesi and Guido Bocci*   Pages 112 - 121 ( 10 )

Abstract:


Background and Objective: The extensive clinical use of capecitabine may be associated with important adverse drug reactions. The aim of this study was to prevent the risk of toxicities in patients who are candidates to capecitabine treatment.

Methods: Pharmacokinetic parameters of 5-fluorouracil (5-FU)/ 5-fluoro-5,6-dihydrouracil (5-FDHU) were examined in 133 cancer patients given a test dose of 5-FU (250 mg/m2) 2 weeks before starting capecitabine treatment. 5-FU and 5-FDHU plasma levels were measured, and related pharmacokinetic parameters were calculated. Toxicities were graded according to Common Toxicity Criteria (CTC) criteria.

Results: Some significant relationships between 5-FU and 5-FDHU pharmacokinetic parameters and capecitabine toxicities were found. Higher values of 5-FU AUC0-∞ and t½β were found in patients who experienced grade ≥2 dermatitis, stomatitis and nausea during capecitabine chemotherapy. Moreover tmax higher than the threshold limit of 15 minutes was predictive for the risk of developing severe diarrhea after the first cycle of capecitabine therapy.

Conclusion: This study suggests a successful approach for preventing moderate/severe toxicities in cancer patients who are candidates to capecitabine treatment by analyzing the 5-FU and 5-FDHU pharmacokinetic parameters after the administration of a reduced 5-FU test dose.

Keywords:

5-Fluorouracil, test dose, pharmacokinetics, capecitabine, cancer, toxicities.

Affiliation:

Division of Pharmacology, Department of Experimental and Clinical Medicine, University of Pisa, Pisa, Department of Medical Oncology, Civil Hospital of Livorno, Istituto Toscano Tumori, Livorno, Division of Pharmacology, Department of Experimental and Clinical Medicine, University of Pisa, Pisa, Division of Pharmacology, Department of Experimental and Clinical Medicine, University of Pisa, Pisa, Oncology Unit 2, University Hospital of Pisa, Pisa, Oncology Unit 2, University Hospital of Pisa, Pisa, Department of Oncology, Civil Hospital of Pontedera, Azienda USL Toscana Nord Ovest, Pisa, Division of Pharmacology, Department of Experimental and Clinical Medicine, University of Pisa, Pisa, Oncology Unit 2, University Hospital of Pisa, Pisa, Division of Pharmacology, Department of Experimental and Clinical Medicine, University of Pisa, Pisa, Division of Pharmacology, Department of Experimental and Clinical Medicine, University of Pisa, Pisa

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