Review
Pharmacology & Pharmacy
Cassandra White, Rodney J. Scott, Christine Paul, Andrew Ziolkowski, David Mossman, Stephen B. Fox, Michael Michael, Stephen Ackland
Summary: Upfront DPYD genotyping can identify high-risk patients for FP treatment and allow personalized dose adjustment, reducing toxicities and improving cost-effectiveness.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Oncology
Antoine Desilets, William McCarvill, Francine Aubin, Houda Bahig, Olivier Ballivy, Danielle Charpentier, Edith Filion, Rahima Jamal, Louise Lambert, Phuc Felix Nguyen-Tan, Charles Vadnais, Xiaoduan Weng, Denis Soulieres
Summary: The combination of carboplatin and 5-FU is effective in treating locoregionally advanced oropharyngeal carcinomas, but DPYD polymorphisms may increase the risk of severe toxicity. Upfront screening for DPYD genotypes can identify patients at risk for 5-FU-related toxicity.
Article
Oncology
Apostolos Tsiachristas, Grant Vallance, Rositsa Koleva-Kolarova, Harriet Taylor, Luke Solomons, Giovanni Rizzo, Catherine Chaytor, Junel Miah, Sarah Wordsworth, A. Bassim Hassan
Summary: The study demonstrated the positive impact of mandatory testing using a DPYD variant panel on reducing toxicity, pain, and hospital costs in cancer patients receiving Capecitabine/5-FU treatment.
Article
Oncology
Catherine Jolivet, Rami Nassabein, Denis Soulieres, Xiaoduan Weng, Carl Amireault, Jean-Pierre Ayoub, Patrice Beauregard, Normand Blais, Christian Carrier, Alexis-Simon Cloutier, Alexandra Desnoyers, Anne-Sophie Lemay, Frederic Lemay, Rasmy Loungnarath, Jacques Jolivet, Francois Letendre, Mustapha Tehfe, Charles Vadnais, Daniel Viens, Francine Aubin
Summary: Fluoropyrimidines are commonly used in chemotherapy for various cancers. This study demonstrates the feasibility of upfront genotyping for DPYD before fluoropyrimidine-based treatment in clinical practice, which can help prevent severe toxicities without delaying treatment initiation. This approach of administering chemotherapy at reduced doses appears to be safe for patients with DPYD*2A mutations.
Article
Biotechnology & Applied Microbiology
Manuela Pinheiro, Ana Peixoto, Patricia Rocha, Catarina Santos, Carla Escudeiro, Isabel Veiga, Miguel Porto, Joana Guerra, Ana Barbosa, Carla Pinto, Patricia Arinto, Adriana Resende, Manuel R. Teixeira
Summary: The study found that 7.4% of 457 patients carried heterozygous DPYD variants, with c.2846A>T being the most common. 15.7% of patients in the post-treatment group had DPYD variants, while only 2.5% of patients in the pretreatment group had a variant. The KASP genotyping assay designed in this study showed 100% genotype concordance with Sanger sequencing results, indicating its reliability for detecting DPYD variants.
PHARMACOGENETICS AND GENOMICS
(2023)
Article
Pharmacology & Pharmacy
Georgia Ragia, Anthi Maslarinou, Natalia Atzemian, Eirini Biziota, Triantafyllia Koukaki, Charalampia Ioannou, Ioanna Balgkouranidou, George Kolios, Stylianos Kakolyris, Nikolaos Xenidis, Kyriakos Amarantidis, Vangelis G. Manolopoulos
Summary: This study aimed to analyze the prevalence of DPYD gene variants and assess their association with FP-induced toxicity in Greek cancer patients. The results showed a significant correlation between DPYD variants and FP-related toxicities.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Oncology
Bhavina B. Sharma, Karan Rai, Heather Blunt, Wenyan Zhao, Tor D. Tosteson, Gabriel A. Brooks
Summary: This study systematically evaluated the risk of treatment-related death associated with DPYD gene variants during fluoropyrimidine chemotherapy, and found that patients with pathogenic DPYD gene variants have a significantly increased risk of treatment-related death.
Review
Health Care Sciences & Services
Woorim Kim, Young-Ah Cho, Dong-Chul Kim, Kyung-Eun Lee
Summary: This study aimed to evaluate the risk of fluoropyrimidine-associated toxicity in patients with DPYD rs1801160 polymorphism. The systematic literature review and meta-analysis revealed an association between rs1801160 polymorphism and fluoropyrimidine-associated toxicity.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Oncology
Gabriel A. Brooks, Stephanie Tapp, Allan T. Daly, Jonathan A. Busam, Anna N. A. Tosteson
Summary: DPYD genotyping as a screening method for preventing rare but severe and sometimes fatal toxicities of fluoropyrimidine chemotherapy is a cost-effective strategy.
CLINICAL COLORECTAL CANCER
(2022)
Article
Health Care Sciences & Services
Soroush Ahmadi Fariman, Zahra Jahangard Rafsanjani, Mandana Hasanzad, Kimia Niksalehi, Shekoufeh Nikfar
Summary: This study aimed to evaluate the cost-effectiveness of preemptive DPYD genotyping to guide fluoropyrimidine therapy in patients with advanced or metastatic colorectal cancer. The results showed that the genotype-guided treatment strategy was cost-saving compared to no screening. However, due to a possible reduction in patient survival with reduced-dose regimens, the genotype-guided treatment strategy was associated with fewer quality-adjusted life-years.
VALUE IN HEALTH REGIONAL ISSUES
(2023)
Article
Pharmacology & Pharmacy
Rositsa Koleva-Kolarova, Heleen Vellekoop, Simone Huygens, Matthijs Versteegh, Maureen Rutten-van Moelken, Laszlo Szilberhorn, Tamas Zelei, Balazs Nagy, Sarah Wordsworth, Apostolos Tsiachristas
Summary: This study aimed to assess the cost-effectiveness of ToxNav (c), a multivariant genetic test, for screening DPYD and personalized chemotherapy dosing in metastatic breast cancer patients in the UK. Results showed that ToxNav (c) was dominant over standard of care, providing additional quality-adjusted life years and cost savings per patient. Sensitivity analysis further supported the effectiveness of the ToxNav (c) strategy.
PERSONALIZED MEDICINE
(2023)
Article
Oncology
Mohammad Salmani, Bayazid Ghaderi, Alan Fotoohi, Ramtin Omid-Shafa'at, Zakaria Vahabzadeh, Omid Fotouhi, Mohammad Abdi
Summary: In this study, we detected the DPYD*2A polymorphism in the Kurdish population for the first time. Our method successfully detected the DPYD*2A variant and, due to its simplicity and cost-effectiveness, it may be considered as an alternative to the current methods, especially in developing countries. Despite the low rate of DPYD*2A polymorphism (0.8%), pharmacogenetic assessment before starting treatment is highly recommended due to its association with a high risk of severe toxicity.
CANCER CHEMOTHERAPY AND PHARMACOLOGY
(2022)
Article
Oncology
Jacob L. van Dam, Quisette P. Janssen, Marc G. Besselink, Marjolein Y. Homs, Hjalmar C. van Santvoort, Geertjan van Tienhoven, Roeland F. de Wilde, Johanna W. Wilmink, Casper H. J. van Eijck, Bas Groot Koerkamp
Summary: This study found that neoadjuvant therapy can improve overall survival in patients with borderline resectable pancreatic cancer. However, more evidence is needed to determine whether it also improves survival in patients with resectable pancreatic cancer.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Oncology
Brandon Chua, Li Min Lim, Joseph Soon Yau Ng, Yan Ma, Hwee Lin Wee, J. Jaime Caro
Summary: Extended genotyping (XGT) for cervical cancer screening, which identifies human papillomavirus (HPV) genotypes beyond HPV16 and HPV18, can provide risk stratification for clinical management. A study in Singapore compared the resource use, cost, and quality-adjusted life years (QALY) of XGT to partial genotyping (PGT). The results showed that XGT was cost-effective, utilized fewer resources, and provided a risk-based approach compared to PGT. This analysis, conducted in an Asian context, could guide the use of XGT in Asia.
Article
Oncology
Xing Gao, Yu-Wen Wen, Joseph Jan Baptist van Lanschot, Yin-Kai Chao
Summary: This study investigated the cost-effectiveness of neoadjuvant therapy followed by surgery (NT) versus upfront surgery followed by adjuvant therapy (US) for patients with esophageal squamous cell carcinoma (ESCC). The results showed that NT is a preferable option for patients with clinical stage 3 ESCC due to its higher cost-effectiveness, while US remains a viable option for stage 2 disease.
ANNALS OF SURGICAL ONCOLOGY
(2022)
Article
Oncology
Robin J. Lurvink, Rudaba Tajzai, Koen P. Rovers, Emma C. E. Wassenaar, Dirk-Jan A. R. Moes, Giulia Pluimakers, Djamila Boerma, Jacobus W. A. Burger, Simon W. Nienhuijs, Ignace H. J. T. de Hingh, Maarten J. Deenen
Summary: This study investigated the pharmacokinetics of oxaliplatin after ePIPAC in 20 patients with unresectable colorectal peritoneal metastases, showing systemic exposure levels comparable to systemic chemotherapy, with urine concentrations gradually decreasing. Future research could focus on a direct comparison between oxaliplatin systemic exposure after ePIPAC and systemic chemotherapy.
ANNALS OF SURGICAL ONCOLOGY
(2021)
Article
Oncology
Koen P. Rovers, Emma C. E. Wassenaar, Robin J. Lurvink, Geert-Jan M. Creemers, Jacobus W. A. Burger, Maartje Los, Clement J. R. Huysentruyt, Gesina van Lijnschoten, Joost Nederend, Max J. Lahaye, Maarten J. Deenen, Marinus J. Wiezer, Simon W. Nienhuijs, Djamila Boerma, Ignace H. J. T. de Hingh
Summary: This study aimed to evaluate the safety and antitumor activity of pressurized intraperitoneal aerosol chemotherapy with oxaliplatin (PIPAC-OX) as a palliative monotherapy for patients with unresectable colorectal peritoneal metastases. The results showed that some major adverse events occurred and minor adverse events were common in these patients, with uncertain clinical relevance of observed biochemical, pathological, and ascites responses.
ANNALS OF SURGICAL ONCOLOGY
(2021)
Letter
Oncology
Koen P. Rovers, Robin J. Lurvink, Maarten J. Deenen, Ignace H. J. T. de Hingh
EUROPEAN JOURNAL OF CANCER
(2021)
Article
Medicine, General & Internal
Robin J. Lurvink, Paulien Rauwerdink, Koen P. Rovers, Emma C. E. Wassenaar, Maarten J. Deenen, Joost Nederend, Clement J. R. Huysentruyt, Iris van 't Erve, Remond J. A. Fijneman, Erik J. R. J. van der Hoeven, Cornelis A. Seldenrijk, Alexander Constantinides, Onno Kranenburg, Maartje Los, Karin H. Herbschleb, Anna M. J. Thijs, Geert-Jan M. Creemers, Jacobus W. A. Burger, Marinus J. Wiezer, Simon W. Nienhuijs, Djamila Boerma, Ignace H. J. T. de Hingh
Summary: This study aims to evaluate the safety, feasibility, antitumour activity, patient-reported outcomes, costs, and pharmacokinetics of first-line bidirectional therapy in patients with isolated unresectable colorectal peritoneal metastases. The primary outcome is the occurrence of grade >= 3 adverse events, and key secondary outcomes include treatment-related characteristics, tumour response, patient-reported outcomes, systemic pharmacokinetics, costs, progression-free survival, and overall survival.
Editorial Material
Oncology
Jeroen F. Schouten, Jeroen Willems, Stefan J. W. J. Sanders, Geert-Jan Creemers, Maarten J. Deenen
Summary: Severe toxicity of fluoropyrimidine drugs is associated with DPD deficiency, screening and dose reduction are common strategies, but new treatment options are still needed. Trifluridine/tipiracil, an independent metabolism drug, may offer a new safe treatment paradigm for DPD-deficient metastatic colorectal cancer patients.
CLINICAL COLORECTAL CANCER
(2021)
Meeting Abstract
Oncology
Emma C. Hulshof, Mirjam de With, Femke M. de Man, Geert-Jan Creemers, Birgit A. L. M. Deiman, Jesse J. Swen, Saskia Houterman, Stijn L. W. Koolen, Marjan Laven, Saskia Luelmo, Ron H. N. van Schaik, Henk-jan Guchelaar, Ron H. J. Mathijssen, Hans Gelderblom, Maarten J. Deenen
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Cell Biology
Maaike van der Lee, William G. Allard, Rolf H. A. M. Vossen, Renee F. Baak-Pablo, Roberta Menafra, Birgit A. L. M. Deiman, Maarten J. Deenen, Patrick Neven, Inger Johansson, Stefano Gastaldello, Magnus Ingelman-Sundberg, Henk-Jan Guchelaar, Jesse J. Swen, Seyed Yahya Anvar
Summary: The study introduces a proof-of-concept approach using continuous-scale assignments to predict CYP2D6 enzyme activity, showing potential for more accurate prediction of individual drug response compared to conventional *-allele approach. This model, trained with complete CYP2D6 gene sequences and tamoxifen metabolism data, explained a higher percentage of interindividual variability in enzyme activity and demonstrated advantages in predicting known and novel allele combinations.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Oncology
Emma C. Hulshof, Mirjam de With, Femke M. de Man, Geert-Jan Creemers, Birgit A. L. M. Deiman, Jesse J. Swen, Saskia Houterman, Stijn L. W. Koolen, Sander Bins, Anna M. J. Thijs, Marjan M. J. Laven, Anke M. Hovels, Saskia A. C. Luelmo, Danny Houtsma, Katerina Shulman, Howard L. McLeod, Ron H. N. van Schaik, Henk-Jan Guchelaar, Ron H. J. Mathijssen, Hans Gelderblom, Maarten J. Deenen
Summary: This study aimed to determine the safety, feasibility, pharmacokinetics, and cost of UGT1A1 genotype-guided dosing of irinotecan. The results showed that UGT1A1 genotype-guided dosing significantly reduces the incidence of febrile neutropenia in UGT1A1 PM patients treated with irinotecan, results in a therapeutically effective systemic drug exposure, and is cost-saving.
EUROPEAN JOURNAL OF CANCER
(2022)
Letter
Oncology
Emma C. Hulshof, Mirjam de With, Geert-Jan Creemers, Henk-Jan Guchelaar, Ron HJ. Mathijssen, Hans Gelderblom, Maarten J. Deenen
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Chemistry, Analytical
Sebastian A. H. van den Wildenberg, Alexander S. Streng, Renske van den Broek, Maarten A. C. Broeren, Maarten J. Deenen, Joost L. J. van Dongen, Maarten A. Hanrath, Chyara Lapre, Luc Brunsveld, Volkher Scharnhorst, Daan van de Kerkhof
Summary: This study presents a novel method for quantification of uracil, dihydrouracil, thymine, and dihydrothymine in human plasma. Stability experiments reveal higher stability of dihydrouracil, thymine, and dihydrothymine compared to uracil, suggesting that the dihydrothymine:dihydrothymine ratio may serve as a more reliable marker for dihydropyrimidine dehydrogenase (DPD) activity. This assay may be used as a diagnostic test in future studies to establish the association between endogenous biomarker concentrations and DPD activity and safety of fluoropyrimidine treatment.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2022)
Review
Biochemistry & Molecular Biology
Emma C. Hulshof, Maarten J. Deenen, Marga Nijenhuis, Bianca Soree, Nienke J. De Boer-Veger, Anne-Marie Buunk, Elisa J. F. Houwink, Arne Risselada, Gerard A. P. J. M. Rongen, Ron H. N. van Schaik, Daan J. Touw, Jan van der Weide, Roos van Westrhenen, Vera H. M. Deneer, Henk-Jan Guchelaar, Jesse J. Swen
Summary: The Dutch Pharmacogenetics Working Group has developed evidence-based guidelines for the optimal starting dose of the anti-cancer drug irinotecan, based on UGT1A1 gene variants. UGT1A1 genotyping is considered essential prior to initiating irinotecan treatment to decrease the risk of severe toxicity.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Correction
Biochemistry & Molecular Biology
Emma C. Hulshof, Maarten J. Deenen, Marga Nijenhuis, Bianca Soree, Nienke J. de Boer-Veger, Anne-Marie Buunk, Elisa J. F. Houwink, Arne Risselada, Gerard A. P. J. M. Rongen, Ron H. N. van Schaik, Daan J. Touw, Jan van der Weide, Roos van Westrhenen, Vera H. M. Deneer, Henk-Jan Guchelaar, Jesse J. Swen
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Pharmacology & Pharmacy
Catharina H. M. Kerskes, Carien J. M. E. van den Eijnde, Albert-Jan L. H. J. Aarnoudse, Rene J. E. Grouls, Birgit A. L. M. Deiman, Maarten J. Deenen
Summary: Patients with CKD stage 3-5 are commonly on multiple medications. This study investigated the benefits of pharmacogenetic testing in evaluating medication therapy for these patients. Pharmacogenetic profiles were determined for adult CKD patients, and medication surveillance was performed to identify gene-drug interactions. Relevance and necessity of pharmacotherapeutic interventions were assessed, resulting in improved pharmacotherapy for 20 patients.
Editorial Material
Pharmacology & Pharmacy
Sofia L. J. Peeters, Maarten J. Deenen, Anna M. J. Thijs, Emma C. Hulshof, Ron H. J. Mathijssen, Hans Gelderblom, Henk-Jan Guchelaar, Jesse J. Swen
Article
Economics
Christine M. Cramer-van der Welle, Bas J. M. Peters, Maarten J. Deenen, Franz M. N. H. Schramel, Ewoudt M. W. van de Garde
Summary: This study shows that overall drug costs were stable over the years, despite a relative increase in first-line treatment costs. Median OS remained at around 8 months from year to year. These trend data are very relevant as background for the assessment of costs and achieved outcomes in the more recent years.
PHARMACOECONOMICS-OPEN
(2021)