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15 results on '"van Kuilenburg, André B.P."'

1. Dihydropyrimidine Dehydrogenase Phenotyping Using Pretreatment Uracil:A Note of Caution Based on a Large Prospective Clinical Study

Author

de With, Mirjam, Knikman, Jonathan, de Man, Femke M., Lunenburg, Carin A.T.C., Henricks, Linda M., van Kuilenburg, André B.P., Maring, Jan G., van Staveren, Maurice C., de Vries, Niels, Rosing, Hilde, Beijnen, Jos H., Pluim, Dick, Modak, Anil, Imholz, Alex L.T., van Schaik, Ron H.N., Schellens, Jan H.M., Gelderblom, Hans, Cats, Annemieke, Guchelaar, Henk Jan, Mathijssen, Ron H.J., Swen, Jesse J., Meulendijks, Didier, de With, Mirjam, Knikman, Jonathan, de Man, Femke M., Lunenburg, Carin A.T.C., Henricks, Linda M., van Kuilenburg, André B.P., Maring, Jan G., van Staveren, Maurice C., de Vries, Niels, Rosing, Hilde, Beijnen, Jos H., Pluim, Dick, Modak, Anil, Imholz, Alex L.T., van Schaik, Ron H.N., Schellens, Jan H.M., Gelderblom, Hans, Cats, Annemieke, Guchelaar, Henk Jan, Mathijssen, Ron H.J., Swen, Jesse J., and Meulendijks, Didier

Abstract

In clinical practice, 25–30% of the patients treated with fluoropyrimidines experience severe fluoropyrimidine-related toxicity. Extensively clinically validated DPYD genotyping tests are available to identify patients at risk of severe toxicity due to decreased activity of dihydropyrimidine dehydrogenase (DPD), the rate limiting enzyme in fluoropyrimidine metabolism. In April 2020, the European Medicines Agency recommended that, as an alternative for DPYD genotype-based testing for DPD deficiency, also phenotype testing based on pretreatment plasma uracil levels is a suitable method to identify patients with DPD deficiency. Although the evidence for genotype-directed dosing of fluoropyrimidines is substantial, the level of evidence supporting plasma uracil levels to predict DPD activity in clinical practice is limited. Notwithstanding this, uracil-based phenotyping is now used in clinical practice in various countries in Europe. We aimed to determine the value of pretreatment uracil levels in predicting DPD deficiency and severe treatment-related toxicity. To this end, we determined pretreatment uracil levels in 955 patients with cancer, and assessed the correlation with DPD activity in peripheral blood mononuclear cells (PBMCs) and fluoropyrimidine-related severe toxicity. We identified substantial issues concerning the use of pretreatment uracil in clinical practice, including large between-center study differences in measured pretreatment uracil levels, most likely as a result of pre-analytical factors. Importantly, we were not able to correlate pretreatment uracil levels with DPD activity nor were uracil levels predictive of severe treatment-related toxicity. We urge that robust clinical validation should first be performed before pretreatment plasma uracil levels are used in clinical practice as part of a dosing strategy for fluoropyrimidines.

Published
2022

2. Liposome-targeted recombinant human acid sphingomyelinase: Production, formulation, and in vitro evaluation

Author

Aldosari, Mohammed H., de Vries, Robert P., Rodriguez, Lucia R., Hesen, Nienke A., Beztsinna, Nataliia, van Kuilenburg, André B.P., Hollak, Carla E.M., Schellekens, Huub, Mastrobattista, Enrico, Aldosari, Mohammed H., de Vries, Robert P., Rodriguez, Lucia R., Hesen, Nienke A., Beztsinna, Nataliia, van Kuilenburg, André B.P., Hollak, Carla E.M., Schellekens, Huub, and Mastrobattista, Enrico

Abstract

Niemann-Pick disease type B is a hereditary rare condition caused by deficiency of the acid sphingomyelinase (ASM) that is needed for lysosomal hydrolysis of sphingomyelin to ceramide and phosphocholine. This deficiency leads to a massive accumulation of sphingomyelin in cells throughout the body, predominantly in the liver, spleen and lungs. Currently, there is no effective treatment available. Olipudase alfa (recombinant human acid sphingomyelinase; rhASM) is an investigational drug that has shown promising results. However, dose-dependent toxicity was observed in mice upon the intravenous administration of rhASM, potentially due to the systemic release of ceramide upon the extracellular degradation of sphingomyelin by rhASM. Using a nanocarrier to deliver the rhASM to cells could improve the therapeutic window by shielding the rhASM to prevent the off-target degradation of sphingomyelin. For this aim, we recombinantly expressed hASM in human cells and loaded it into different liposomal formulations at a drug-to-lipid ratio of 4% (w/w). Among four formulations, the liposomal rhASM formulation with the composition DPPC:DOPS:BMP:CHOL:DiD (59:20:10:10:1 mol%) was selected because of its superiority concerning the encapsulation efficiency of rhASM (21%) and cellular uptake by fibroblasts and macrophages. The selected liposomal rhASM formulation significantly reduced the accumulated lyso-sphingomyelin in NPD-B fibroblasts by 71%, part of this effect was stimulated by the used lipids, compared to 55% when using the free rhASM enzyme. More importantly, the undesired extracellular degradation of sphingomyelin was reduced when using the selected liposomal rhASM by 61% relative to the free rhASM. The presented in vitro data indicate that the liposomal rhASM is effective and may provide a safer intervention than free rhASM.

Published
2019

3. A cost analysis of upfront DPYD genotype–guided dose individualisation in fluoropyrimidine-based anticancer therapy

Author

Henricks, Linda M., Lunenburg, Carin A.T.C., de Man, Femke M., Meulendijks, Didier, Frederix, Geert W.J., Kienhuis, Emma, Creemers, Geert Jan, Baars, Arnold, Dezentjé, Vincent O., Imholz, Alexander L.T., Jeurissen, Frank J.F., Portielje, Johanna E.A., Jansen, Rob L.H., Hamberg, Paul, ten Tije, Albert J., Droogendijk, Helga J., Koopman, Miriam, Nieboer, Peter, van de Poel, Marlène H.W., Mandigers, Caroline M.P.W., Rosing, Hilde, Beijnen, Jos H., van Werkhoven, Erik, van Kuilenburg, André B.P., van Schaik, Ron H.N., Mathijssen, Ron H.J., Swen, Jesse J., Gelderblom, Hans, Cats, Annemieke, Guchelaar, Henk Jan, Schellens, Jan H.M., Henricks, Linda M., Lunenburg, Carin A.T.C., de Man, Femke M., Meulendijks, Didier, Frederix, Geert W.J., Kienhuis, Emma, Creemers, Geert Jan, Baars, Arnold, Dezentjé, Vincent O., Imholz, Alexander L.T., Jeurissen, Frank J.F., Portielje, Johanna E.A., Jansen, Rob L.H., Hamberg, Paul, ten Tije, Albert J., Droogendijk, Helga J., Koopman, Miriam, Nieboer, Peter, van de Poel, Marlène H.W., Mandigers, Caroline M.P.W., Rosing, Hilde, Beijnen, Jos H., van Werkhoven, Erik, van Kuilenburg, André B.P., van Schaik, Ron H.N., Mathijssen, Ron H.J., Swen, Jesse J., Gelderblom, Hans, Cats, Annemieke, Guchelaar, Henk Jan, and Schellens, Jan H.M.

Published
2019

4. A cost analysis of upfront DPYD genotype–guided dose individualisation in fluoropyrimidine-based anticancer therapy

Author

Henricks, Linda M., Lunenburg, Carin A.T.C., de Man, Femke M., Meulendijks, Didier, Frederix, Geert W.J., Kienhuis, Emma, Creemers, Geert Jan, Baars, Arnold, Dezentjé, Vincent O., Imholz, Alexander L.T., Jeurissen, Frank J.F., Portielje, Johanna E.A., Jansen, Rob L.H., Hamberg, Paul, ten Tije, Albert J., Droogendijk, Helga J., Koopman, Miriam, Nieboer, Peter, van de Poel, Marlène H.W., Mandigers, Caroline M.P.W., Rosing, Hilde, Beijnen, Jos H., van Werkhoven, Erik, van Kuilenburg, André B.P., van Schaik, Ron H.N., Mathijssen, Ron H.J., Swen, Jesse J., Gelderblom, Hans, Cats, Annemieke, Guchelaar, Henk Jan, Schellens, Jan H.M., Henricks, Linda M., Lunenburg, Carin A.T.C., de Man, Femke M., Meulendijks, Didier, Frederix, Geert W.J., Kienhuis, Emma, Creemers, Geert Jan, Baars, Arnold, Dezentjé, Vincent O., Imholz, Alexander L.T., Jeurissen, Frank J.F., Portielje, Johanna E.A., Jansen, Rob L.H., Hamberg, Paul, ten Tije, Albert J., Droogendijk, Helga J., Koopman, Miriam, Nieboer, Peter, van de Poel, Marlène H.W., Mandigers, Caroline M.P.W., Rosing, Hilde, Beijnen, Jos H., van Werkhoven, Erik, van Kuilenburg, André B.P., van Schaik, Ron H.N., Mathijssen, Ron H.J., Swen, Jesse J., Gelderblom, Hans, Cats, Annemieke, Guchelaar, Henk Jan, and Schellens, Jan H.M.

Published
2019

5. Liposome-targeted recombinant human acid sphingomyelinase: Production, formulation, and in vitro evaluation

Author

Afd Pharmaceutics, Afd Chemical Biology and Drug Discovery, Pharmaceutics, Chemical Biology and Drug Discovery, Aldosari, Mohammed H., de Vries, Robert P., Rodriguez, Lucia R., Hesen, Nienke A., Beztsinna, Nataliia, van Kuilenburg, André B.P., Hollak, Carla E.M., Schellekens, Huub, Mastrobattista, Enrico, Afd Pharmaceutics, Afd Chemical Biology and Drug Discovery, Pharmaceutics, Chemical Biology and Drug Discovery, Aldosari, Mohammed H., de Vries, Robert P., Rodriguez, Lucia R., Hesen, Nienke A., Beztsinna, Nataliia, van Kuilenburg, André B.P., Hollak, Carla E.M., Schellekens, Huub, and Mastrobattista, Enrico

Published
2019

6. A cost analysis of upfront DPYD genotype–guided dose individualisation in fluoropyrimidine-based anticancer therapy

Author

Henricks, Linda M., Lunenburg, Carin A.T.C., de Man, Femke M., Meulendijks, Didier, Frederix, Geert W.J., Kienhuis, Emma, Creemers, Geert Jan, Baars, Arnold, Dezentjé, Vincent O., Imholz, Alexander L.T., Jeurissen, Frank J.F., Portielje, Johanna E.A., Jansen, Rob L.H., Hamberg, Paul, ten Tije, Albert J., Droogendijk, Helga J., Koopman, Miriam, Nieboer, Peter, van de Poel, Marlène H.W., Mandigers, Caroline M.P.W., Rosing, Hilde, Beijnen, Jos H., van Werkhoven, Erik, van Kuilenburg, André B.P., van Schaik, Ron H.N., Mathijssen, Ron H.J., Swen, Jesse J., Gelderblom, Hans, Cats, Annemieke, Guchelaar, Henk Jan, Schellens, Jan H.M., Henricks, Linda M., Lunenburg, Carin A.T.C., de Man, Femke M., Meulendijks, Didier, Frederix, Geert W.J., Kienhuis, Emma, Creemers, Geert Jan, Baars, Arnold, Dezentjé, Vincent O., Imholz, Alexander L.T., Jeurissen, Frank J.F., Portielje, Johanna E.A., Jansen, Rob L.H., Hamberg, Paul, ten Tije, Albert J., Droogendijk, Helga J., Koopman, Miriam, Nieboer, Peter, van de Poel, Marlène H.W., Mandigers, Caroline M.P.W., Rosing, Hilde, Beijnen, Jos H., van Werkhoven, Erik, van Kuilenburg, André B.P., van Schaik, Ron H.N., Mathijssen, Ron H.J., Swen, Jesse J., Gelderblom, Hans, Cats, Annemieke, Guchelaar, Henk Jan, and Schellens, Jan H.M.

Published
2019

7. Liposome-targeted recombinant human acid sphingomyelinase: Production, formulation, and in vitro evaluation

Author

Afd Pharmaceutics, Afd Chemical Biology and Drug Discovery, Pharmaceutics, Chemical Biology and Drug Discovery, Aldosari, Mohammed H., de Vries, Robert P., Rodriguez, Lucia R., Hesen, Nienke A., Beztsinna, Nataliia, van Kuilenburg, André B.P., Hollak, Carla E.M., Schellekens, Huub, Mastrobattista, Enrico, Afd Pharmaceutics, Afd Chemical Biology and Drug Discovery, Pharmaceutics, Chemical Biology and Drug Discovery, Aldosari, Mohammed H., de Vries, Robert P., Rodriguez, Lucia R., Hesen, Nienke A., Beztsinna, Nataliia, van Kuilenburg, André B.P., Hollak, Carla E.M., Schellekens, Huub, and Mastrobattista, Enrico

Published
2019

8. A cost analysis of upfront DPYD genotype–guided dose individualisation in fluoropyrimidine-based anticancer therapy

Author

Apotheek Opleiding, UMC Utrecht, HEE, Child Health, JC onderzoeksprogramma Methodologie, MS Medische Oncologie, Henricks, Linda M., Lunenburg, Carin A.T.C., de Man, Femke M., Meulendijks, Didier, Frederix, Geert W.J., Kienhuis, Emma, Creemers, Geert Jan, Baars, Arnold, Dezentjé, Vincent O., Imholz, Alexander L.T., Jeurissen, Frank J.F., Portielje, Johanna E.A., Jansen, Rob L.H., Hamberg, Paul, ten Tije, Albert J., Droogendijk, Helga J., Koopman, Miriam, Nieboer, Peter, van de Poel, Marlène H.W., Mandigers, Caroline M.P.W., Rosing, Hilde, Beijnen, Jos H., van Werkhoven, Erik, van Kuilenburg, André B.P., van Schaik, Ron H.N., Mathijssen, Ron H.J., Swen, Jesse J., Gelderblom, Hans, Cats, Annemieke, Guchelaar, Henk Jan, Schellens, Jan H.M., Apotheek Opleiding, UMC Utrecht, HEE, Child Health, JC onderzoeksprogramma Methodologie, MS Medische Oncologie, Henricks, Linda M., Lunenburg, Carin A.T.C., de Man, Femke M., Meulendijks, Didier, Frederix, Geert W.J., Kienhuis, Emma, Creemers, Geert Jan, Baars, Arnold, Dezentjé, Vincent O., Imholz, Alexander L.T., Jeurissen, Frank J.F., Portielje, Johanna E.A., Jansen, Rob L.H., Hamberg, Paul, ten Tije, Albert J., Droogendijk, Helga J., Koopman, Miriam, Nieboer, Peter, van de Poel, Marlène H.W., Mandigers, Caroline M.P.W., Rosing, Hilde, Beijnen, Jos H., van Werkhoven, Erik, van Kuilenburg, André B.P., van Schaik, Ron H.N., Mathijssen, Ron H.J., Swen, Jesse J., Gelderblom, Hans, Cats, Annemieke, Guchelaar, Henk Jan, and Schellens, Jan H.M.

Published
2019

9. Liposome-targeted recombinant human acid sphingomyelinase: Production, formulation, and in vitro evaluation

Author

Afd Pharmaceutics, Afd Chemical Biology and Drug Discovery, Pharmaceutics, Chemical Biology and Drug Discovery, Aldosari, Mohammed H., de Vries, Robert P., Rodriguez, Lucia R., Hesen, Nienke A., Beztsinna, Nataliia, van Kuilenburg, André B.P., Hollak, Carla E.M., Schellekens, Huub, Mastrobattista, Enrico, Afd Pharmaceutics, Afd Chemical Biology and Drug Discovery, Pharmaceutics, Chemical Biology and Drug Discovery, Aldosari, Mohammed H., de Vries, Robert P., Rodriguez, Lucia R., Hesen, Nienke A., Beztsinna, Nataliia, van Kuilenburg, André B.P., Hollak, Carla E.M., Schellekens, Huub, and Mastrobattista, Enrico

Published
2019

10. DPYD genotype-guided dose individualisation of fluoropyrimidine therapy in patients with cancer : a prospective safety analysis

Author

Henricks, Linda M., Lunenburg, Carin A.T.C., de Man, Femke M., Meulendijks, Didier, Frederix, Geert W.J., Kienhuis, Emma, Creemers, Geert Jan, Baars, Arnold, Dezentjé, Vincent O., Imholz, Alexander L.T., Jeurissen, Frank J.F., Portielje, Johanna E.A., Jansen, Rob L.H., Hamberg, Paul, ten Tije, Albert J., Droogendijk, Helga J., Koopman, Miriam, Nieboer, Peter, van de Poel, Marlène H.W., Mandigers, Caroline M.P.W., Rosing, Hilde, Beijnen, Jos H., Werkhoven, Erik van, van Kuilenburg, André B.P., van Schaik, Ron H.N., Mathijssen, Ron H.J., Swen, Jesse J., Gelderblom, Hans, Cats, Annemieke, Guchelaar, Henk Jan, Schellens, Jan H.M., Henricks, Linda M., Lunenburg, Carin A.T.C., de Man, Femke M., Meulendijks, Didier, Frederix, Geert W.J., Kienhuis, Emma, Creemers, Geert Jan, Baars, Arnold, Dezentjé, Vincent O., Imholz, Alexander L.T., Jeurissen, Frank J.F., Portielje, Johanna E.A., Jansen, Rob L.H., Hamberg, Paul, ten Tije, Albert J., Droogendijk, Helga J., Koopman, Miriam, Nieboer, Peter, van de Poel, Marlène H.W., Mandigers, Caroline M.P.W., Rosing, Hilde, Beijnen, Jos H., Werkhoven, Erik van, van Kuilenburg, André B.P., van Schaik, Ron H.N., Mathijssen, Ron H.J., Swen, Jesse J., Gelderblom, Hans, Cats, Annemieke, Guchelaar, Henk Jan, and Schellens, Jan H.M.

Published
2018

11. DPYD genotype-guided dose individualisation of fluoropyrimidine therapy in patients with cancer : a prospective safety analysis

Author

Henricks, Linda M., Lunenburg, Carin A.T.C., de Man, Femke M., Meulendijks, Didier, Frederix, Geert W.J., Kienhuis, Emma, Creemers, Geert Jan, Baars, Arnold, Dezentjé, Vincent O., Imholz, Alexander L.T., Jeurissen, Frank J.F., Portielje, Johanna E.A., Jansen, Rob L.H., Hamberg, Paul, ten Tije, Albert J., Droogendijk, Helga J., Koopman, Miriam, Nieboer, Peter, van de Poel, Marlène H.W., Mandigers, Caroline M.P.W., Rosing, Hilde, Beijnen, Jos H., Werkhoven, Erik van, van Kuilenburg, André B.P., van Schaik, Ron H.N., Mathijssen, Ron H.J., Swen, Jesse J., Gelderblom, Hans, Cats, Annemieke, Guchelaar, Henk Jan, Schellens, Jan H.M., Henricks, Linda M., Lunenburg, Carin A.T.C., de Man, Femke M., Meulendijks, Didier, Frederix, Geert W.J., Kienhuis, Emma, Creemers, Geert Jan, Baars, Arnold, Dezentjé, Vincent O., Imholz, Alexander L.T., Jeurissen, Frank J.F., Portielje, Johanna E.A., Jansen, Rob L.H., Hamberg, Paul, ten Tije, Albert J., Droogendijk, Helga J., Koopman, Miriam, Nieboer, Peter, van de Poel, Marlène H.W., Mandigers, Caroline M.P.W., Rosing, Hilde, Beijnen, Jos H., Werkhoven, Erik van, van Kuilenburg, André B.P., van Schaik, Ron H.N., Mathijssen, Ron H.J., Swen, Jesse J., Gelderblom, Hans, Cats, Annemieke, Guchelaar, Henk Jan, and Schellens, Jan H.M.

Published
2018

12. DPYD genotype-guided dose individualisation of fluoropyrimidine therapy in patients with cancer : a prospective safety analysis

Author

Henricks, Linda M., Lunenburg, Carin A.T.C., de Man, Femke M., Meulendijks, Didier, Frederix, Geert W.J., Kienhuis, Emma, Creemers, Geert Jan, Baars, Arnold, Dezentjé, Vincent O., Imholz, Alexander L.T., Jeurissen, Frank J.F., Portielje, Johanna E.A., Jansen, Rob L.H., Hamberg, Paul, ten Tije, Albert J., Droogendijk, Helga J., Koopman, Miriam, Nieboer, Peter, van de Poel, Marlène H.W., Mandigers, Caroline M.P.W., Rosing, Hilde, Beijnen, Jos H., Werkhoven, Erik van, van Kuilenburg, André B.P., van Schaik, Ron H.N., Mathijssen, Ron H.J., Swen, Jesse J., Gelderblom, Hans, Cats, Annemieke, Guchelaar, Henk Jan, Schellens, Jan H.M., Henricks, Linda M., Lunenburg, Carin A.T.C., de Man, Femke M., Meulendijks, Didier, Frederix, Geert W.J., Kienhuis, Emma, Creemers, Geert Jan, Baars, Arnold, Dezentjé, Vincent O., Imholz, Alexander L.T., Jeurissen, Frank J.F., Portielje, Johanna E.A., Jansen, Rob L.H., Hamberg, Paul, ten Tije, Albert J., Droogendijk, Helga J., Koopman, Miriam, Nieboer, Peter, van de Poel, Marlène H.W., Mandigers, Caroline M.P.W., Rosing, Hilde, Beijnen, Jos H., Werkhoven, Erik van, van Kuilenburg, André B.P., van Schaik, Ron H.N., Mathijssen, Ron H.J., Swen, Jesse J., Gelderblom, Hans, Cats, Annemieke, Guchelaar, Henk Jan, and Schellens, Jan H.M.

Published
2018

13. DPYD genotype-guided dose individualisation of fluoropyrimidine therapy in patients with cancer: a prospective safety analysis

Author

Apotheek Opleiding, UMC Utrecht, HEE, Child Health, JC onderzoeksprogramma Methodologie, MS Medische Oncologie, Henricks, Linda M., Lunenburg, Carin A.T.C., de Man, Femke M., Meulendijks, Didier, Frederix, Geert W.J., Kienhuis, Emma, Creemers, Geert Jan, Baars, Arnold, Dezentjé, Vincent O., Imholz, Alexander L.T., Jeurissen, Frank J.F., Portielje, Johanna E.A., Jansen, Rob L.H., Hamberg, Paul, ten Tije, Albert J., Droogendijk, Helga J., Koopman, Miriam, Nieboer, Peter, van de Poel, Marlène H.W., Mandigers, Caroline M.P.W., Rosing, Hilde, Beijnen, Jos H., Werkhoven, Erik van, van Kuilenburg, André B.P., van Schaik, Ron H.N., Mathijssen, Ron H.J., Swen, Jesse J., Gelderblom, Hans, Cats, Annemieke, Guchelaar, Henk Jan, Schellens, Jan H.M., Apotheek Opleiding, UMC Utrecht, HEE, Child Health, JC onderzoeksprogramma Methodologie, MS Medische Oncologie, Henricks, Linda M., Lunenburg, Carin A.T.C., de Man, Femke M., Meulendijks, Didier, Frederix, Geert W.J., Kienhuis, Emma, Creemers, Geert Jan, Baars, Arnold, Dezentjé, Vincent O., Imholz, Alexander L.T., Jeurissen, Frank J.F., Portielje, Johanna E.A., Jansen, Rob L.H., Hamberg, Paul, ten Tije, Albert J., Droogendijk, Helga J., Koopman, Miriam, Nieboer, Peter, van de Poel, Marlène H.W., Mandigers, Caroline M.P.W., Rosing, Hilde, Beijnen, Jos H., Werkhoven, Erik van, van Kuilenburg, André B.P., van Schaik, Ron H.N., Mathijssen, Ron H.J., Swen, Jesse J., Gelderblom, Hans, Cats, Annemieke, Guchelaar, Henk Jan, and Schellens, Jan H.M.

Published
2018

14. Diagnostic and therapeutic strategies for fluoropyrimidine treatment of patients carrying multiple DPYD variants

Author

Lunenburg, Carin A.T.C., Henricks, Linda M., van Kuilenburg, André B.P., Mathijssen, Ron H.J., Schellens, Jan H.M., Gelderblom, Hans, Guchelaar, Henk Jan, Swen, Jesse J., Lunenburg, Carin A.T.C., Henricks, Linda M., van Kuilenburg, André B.P., Mathijssen, Ron H.J., Schellens, Jan H.M., Gelderblom, Hans, Guchelaar, Henk Jan, and Swen, Jesse J.

Abstract

DPYD genotyping prior to fluoropyrimidine treatment is increasingly implemented in clinical care. Without phasing information (i.e., allelic location of variants), current genotype-based dosing guidelines cannot be applied to patients carrying multiple DPYD variants. The primary aim of this study is to examine diagnostic and therapeutic strategies for fluoropyrimidine treatment of patients carrying multiple DPYD variants. A case series of patients carrying multiple DPYD variants is presented. Different genotyping techniques were used to determine phasing information. Phenotyping was performed by dihydropyrimidine dehydrogenase (DPD) enzyme activity measurements. Publicly available databases were queried to explore the frequency and phasing of variants of patients carrying multiple DPYD variants. Four out of seven patients carrying multiple DPYD variants received a full dose of fluoropyrimidines and experienced severe toxicity. Phasing information could be retrieved for four patients. In three patients, variants were located on two different alleles, i.e., in trans. Recommended dose reductions based on the phased genotype differed from the phenotype-derived dose reductions in three out of four cases. Data from publicly available databases show that the frequency of patients carrying multiple DPYD variants is low (< 0.2%), but higher than the frequency of the commonly tested DPYD*13 variant (0.1%). Patients carrying multiple DPYD variants are at high risk of developing severe toxicity. Additional analyses are required to determine the correct dose of fluoropyrimidine treatment. In patients carrying multiple DPYD variants, we recommend that a DPD phenotyping assay be carried out to determine a safe starting dose.

Published
2018

15. Catecholamines profiles at diagnosis: Increased diagnostic sensitivity and correlation with biological and clinical features in neuroblastoma patients

Author

PMC Research, Onderzoek Beeld, Cancer, Verly, Iedan R.N., van Kuilenburg, André B.P., Abeling, Nico G.G.M., Goorden, Susan M.I., Fiocco, Marta, Vaz, Frédéric M., van Noesel, Max M., Zwaan, C. Michel, Kaspers, Gert Jan L., Merks, Johannes H.M., Caron, Huib N., Tytgat, Godelieve A.M., PMC Research, Onderzoek Beeld, Cancer, Verly, Iedan R.N., van Kuilenburg, André B.P., Abeling, Nico G.G.M., Goorden, Susan M.I., Fiocco, Marta, Vaz, Frédéric M., van Noesel, Max M., Zwaan, C. Michel, Kaspers, Gert Jan L., Merks, Johannes H.M., Caron, Huib N., and Tytgat, Godelieve A.M.

Published
2017

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