DPD-deficiency and capecitabine-related toxicity: clinical relevance of measuring DPD-activity.

Roos, S. (Sophie) (2014) DPD-deficiency and capecitabine-related toxicity: clinical relevance of measuring DPD-activity. thesis, Medicine.

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Abstract

Background. Capecitabine (Xeloda ®) is a widely used oral chemotherapeutic drug, which potentially could cause severe toxicity. This might be due to a deficiency of the enzyme dihydropyrimidine dehydrogenase (DPD). Therefore it could be useful to screen every patient for DPD-deficiency before start of chemotherapy. The aim of this study was to determine the clinical relevance of DPD-deficiency in patients treated with capecitabine, by determining a cutoff level to predict toxicity and by defining the consequences concerning interventions of treatment. Method. We included adult patients treated with capecitabine from October 2011 until March 2014 in two hospitals in the Netherlands. Two equal groups were identified, consisting of patients of whom the DPD-activity was determined or not. From all patients, data concerning capecitabine-related toxicity, interventions and basic demographic data were collected from digital records. Results. A total of 164 patients were analysed, of whom in 77 (47%) cases the DPD-activity was determined. DPD-deficiency was seen in 12 (16%) patients. The best cut-off value with a sensitivity of 63% and a specificity of 61% was a DPD-activity of 9,65 nmol/mg/h. There was no significant difference in mean DPD-activity between the different grades of toxicity. Independent of DPD-measuring, reducing the dose of capecitabine decreased the grade of toxicity. Conclusion. No cut-off value to define DPD-deficiency based on the degree of DPD-activity and the grade of toxicity could be identified. Furthermore, measuring the DPD-activity played a minor role concerning interventions after the occurrence of toxicity. This study points out the doubt if determining the DPD-activity is a genuinely added parameter to predict toxicity in patients undergoing chemotherapy with capecitabine. Further studies are warranted to clarify the importance of the measurement of DPD-activity.

Item Type:	Thesis (Thesis)
Supervisor name:	Imholz, Dr. A. and Deventer Ziekenhuis
Supervisor name:	Houtenbos, Dr. I. and Eskes, Dr. A.M. and Kennemer Gasthuis
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:59
Last Modified:	25 Jun 2020 10:59
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/1974

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