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TDM oncology

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https://www.readbyqxmd.com/read/28937535/validation-of-a-commercial-assay-and-decision-support-tool-for-routine-paclitaxel-therapeutic-drug-monitoring-tdm
#1
Markus Joerger, Stefanie Kraff, Ulrich Jaehde, Ralf A Hilger, Jodi B Courtney, Daniel J Cline, Sonali Jog, Irina Baburina, M C Miller, Salvatore J Salamone
BACKGROUND: The value of therapeutic drug monitoring (TDM) for paclitaxel was recently demonstrated in the largest TDM trial ever conducted in oncology. The trial demonstrated significant reduction in neuropathy when using TDM. Dose adjustment for paclitaxel was based on time above a threshold concentration (Tc>0.05). Tc>0.05 must be calculated with a pharmacokinetic model and complex non-linear mixed effects (NLME) software. The use of the software and chromatographic methods to measure paclitaxel require specialized expertise...
September 18, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28766887/a-cost-analysis-of-individualized-asparaginase-treatment-in-pediatric-acute-lymphoblastic-leukemia
#2
Robin Q H Kloos, Carin A Uyl-de Groot, Raphaële R L van Litsenburg, Gertjan J L Kaspers, Rob Pieters, Inge M van der Sluis
BACKGROUND: Therapeutic drug monitoring (TDM) of asparaginase is necessary to respond to variability in asparaginase activity levels, detect silent inactivation, and distinguish between real allergies and allergic-like reactions with and without asparaginase neutralization, respectively. In this study, the costs of an individualized and fixed asparaginase dosing schedule were compared. PROCEDURE: Patients, treated according to the Dutch Childhood Oncology Group ALL-11 protocol (individualized PEGasparaginase treatment, starting dose: 1,500 IU/m(2) ) or ALL-10 protocol (native Escherichia coli asparaginase followed by 2,500 IU/m(2) PEGasparaginase), were included...
August 2, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28724346/biosensing-technologies-for-therapeutic-drug-monitoring
#3
Anna Meneghello, Stefano Tartaggia, Maria Domenica Alvau, Federico Polo, Giuseppe Toffoli
Therapeutic drug monitoring (TDM) is the clinical practice of measuring pharmaceutical drug concentrations in patients' biofluids at designated intervals to allow a close and timely control of their dosage. This practice allows for rapid medical intervention in case of toxicity-related issues and/or adjustment of dosage to better fit the therapeutic demand. Currently, TDM is performed in centralized laboratories employing instruments, such as immunoassay analyzers and mass spectrometers that can be run only by trained personnel...
July 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28634655/effect-of-adherence-on-pharmacokinetic-pharmacodynamic-relationships-of-oral-targeted-anticancer-drugs
#4
Evelina Cardoso, Chantal Csajka, Marie P Schneider, Nicolas Widmer
The emergence of oral targeted anticancer agents transformed several cancers into chronic conditions with a need for long-term oral treatment. Although cancer is a life-threatening condition, oncology medication adherence-the extent to which a patient follows the drug regimen that is intended by the prescriber-can be suboptimal in the long term, as in any other chronic disease. Poor adherence can impact negatively on clinical outcomes, notably because most of these drugs are given as a standard non-individualized dosage despite marked inter-individual variabilities that can lead to toxic or inefficacious drug concentrations...
June 20, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28533244/a-population-pharmacokinetic-model-of-gentamicin-in-pediatric-oncology-patients-to-facilitate-personalized-dosing
#5
C C Llanos-Paez, C E Staatz, R Lawson, S Hennig
To ensure the safe and effective dosing of gentamicin in children, therapeutic drug monitoring (TDM) is recommended. TDM utilizing Bayesian forecasting software is recommended but is unavailable, as no population model that describes the pharmacokinetics of gentamicin in pediatric oncology patients exists. This study aimed to develop and externally evaluate a population pharmacokinetic model of gentamicin to support personalized dosing in pediatric oncology patients. A nonlinear mixed-effect population pharmacokinetic model was developed from retrospective data...
August 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28489727/pharmacology-of-thiopurine-therapy-in-inflammatory-bowel-disease-and-complete-blood-cell-count-outcomes-a-5-year-database-study
#6
Berrie Meijer, Abraham J Wilhelm, Chris J J Mulder, Gerd Bouma, Adriaan A van Bodegraven, Nanne K H de Boer
BACKGROUND: Thiopurines are the prerequisite for immunomodulation in inflammatory bowel disease (IBD) therapy. When administered in high (oncological) dose, thiopurine metabolites act as purine antagonists, causing DNA-strand breakage and myelotoxicity. In lower IBD dosages, the mode of action is primarily restricted to anti-inflammatory effects. Then, myelosuppression and hepatotoxicity are the most common adverse events of thiopurines. The aim of this study was to assess the effect of thiopurine metabolites on hematologic and hepatic parameters and to determine which patient characteristics are related to generation of thiopurine metabolites...
August 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28473246/towards-therapeutic-drug-monitoring-of-everolimus-in-cancer-results-of-an-exploratory-study-of-exposure-effect-relationship
#7
Marine Deppenweiler, Sabrina Falkowski, Franck Saint-Marcoux, Caroline Monchaud, Nicolas Picard, Marie-Laure Laroche, Nicole Tubiana-Mathieu, Laurence Venat-Bouvet, Pierre Marquet, Jean-Baptiste Woillard
INTRODUCTION: Therapeutic drug monitoring (TDM) of everolimus is not performed in oncology and no trough level (C0) target has been yet defined. The aim of this study was to determine everolimus C0 target for toxicity and efficacy. MATERIALS AND METHODS: Clinical, biological and radiologic data from 54 patients were collected. Toxicity event was defined by termination, temporary interruption and/or dose reduction of everolimus while efficacy was defined as progression-free survival...
May 1, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27446421/therapeutic-drug-monitoring-and-tyrosine-kinase-inhibitors
#8
Pauline Herviou, Emilie Thivat, Damien Richard, Lucie Roche, Joyce Dohou, Mélanie Pouget, Alain Eschalier, Xavier Durando, Nicolas Authier
The therapeutic activity of drugs can be optimized by establishing an individualized dosage, based on the measurement of the drug concentration in the serum, particularly if the drugs are characterized by an inter-individual variation in pharmacokinetics that results in an under- or overexposure to treatment. In recent years, several tyrosine kinase inhibitors (TKIs) have been developed to block intracellular signaling pathways in tumor cells. These oral drugs are candidates for therapeutic drug monitoring (TDM) due to their high inter-individual variability for therapeutic and toxic effects...
August 2016: Oncology Letters
https://www.readbyqxmd.com/read/27270831/evaluation-of-clinical-pharmacists-interventions-in-the-czech-republic
#9
Jitka Rychlíčková, Jan Šaloun, Jana Gregorová
STUDY OBJECTIVES: To determine the frequency of interventions, categorized by type of intervention and therapeutic class, made by a team of four clinical pharmacists over a 1-year period, and to assess the potential economic impact of these interventions. DESIGN: Prospective analysis. SETTING: Large medical center in Prague, Czech Republic. PATIENTS: A total of 9153 adults who were admitted to the general surgery, infectious diseases, oncology, orthopedics, and thoracic surgery and respiratory medicine services between January 1, 2014, and December 31, 2014...
July 2016: Pharmacotherapy
https://www.readbyqxmd.com/read/27217046/therapeutic-drug-monitoring-of-5-fluorouracil
#10
REVIEW
James J Lee, Jan H Beumer, Edward Chu
PURPOSE: For over 50 years, 5-FU has played a critical role in the systemic chemotherapy of cancer patients. 5-FU serves as the main backbone of combination chemotherapy for patients with colorectal cancer in both the adjuvant and metastatic disease settings. Herein, we review the current status of 5-FU therapeutic drug monitoring (TDM) and discuss its potential role in the clinical practice setting. METHOD: PubMed and abstracts from the American Society of Clinical Oncology were searched up through September 2015 for clinical data relating to 5-FU TDM...
September 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27065859/design-and-testing-of-an-ehr-integrated-busulfan-pharmacokinetic-decision-support-tool-for-the-point-of-care-clinician
#11
Susan M Abdel-Rahman, Matthew L Breitkreutz, Charlie Bi, Brett J Matzuka, Jignesh Dalal, K Leigh Casey, Uttam Garg, Sara Winkle, J Steven Leeder, JeanAnn Breedlove, Brian Rivera
BACKGROUND: Busulfan demonstrates a narrow therapeutic index for which clinicians routinely employ therapeutic drug monitoring (TDM). However, operationalizing TDM can be fraught with inefficiency. We developed and tested software encoding a clinical decision support tool (DST) that is embedded into our electronic health record (EHR) and designed to streamline the TDM process for our oncology partners. METHODS: Our development strategy was modeled based on the features associated with successful DSTs...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27055173/toward-sers-based-point-of-care-approaches-for-therapeutic-drug-monitoring-the-case-of-methotrexate
#12
Stefano Fornasaro, Silvia Dalla Marta, Marco Rabusin, Alois Bonifacio, Valter Sergo
To date, in spite of their toxicity, the plasmatic concentration of most chemotherapeutic drugs is difficult to monitor in oncological patients, because their quantitative determination is expensive and time consuming. This contribution reports a first attempt for the direct quantitative determination of a chemotherapeutic drug in human serum samples by means of Surface Enhanced Raman Spectroscopy (SERS). In this study, SERS substrates constituted by Au nanoparticles deposited on paper by a simple dipping method have been used for rapid (few minutes) analysis of diluted human serum spiked with different concentrations of methotrexate, MTX...
June 23, 2016: Faraday Discussions
https://www.readbyqxmd.com/read/26558811/the-clinical-significance-of-voriconazole-therapeutic-drug-monitoring-in-children-with-invasive-fungal-infections
#13
Hyun Mi Kang, Hoan Jong Lee, Eun Young Cho, Kyung-Sang Yu, Hyunju Lee, Ji Won Lee, Hyoung Jin Kang, Kyung Duk Park, Hee Young Shin, Eun Hwa Choi
Voriconazole is an antifungal drug used to treat fungal infections. This was a retrospective study of 61 children with hemato-oncologic diseases or solid organ transplantation who were administered voriconazole for invasive fungal infections. Of the 61 patients, 31 (50.8%) were in the therapeutic drug monitoring (TDM) group, and 30 (49.2%) were in the non-TDM group. At 12 weeks, treatment failure rate in the non-TDM group was higher than the TDM group (78.6% versus 40.0%, p = 0.038). Drug discontinuation due to adverse events was less frequent in the TDM group than the non-TDM group (26...
2015: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/26265133/therapeutic-drug-monitoring-of-monoclonal-antibodies-in-inflammatory-and-malignant-disease-translating-tnf-%C3%AE-experience-to-oncology
#14
REVIEW
T H Oude Munnink, M J Henstra, L I Segerink, K L L Movig, P Brummelhuis-Visser
Lack of response to monoclonal antibodies (mAbs) has been associated with inadequate mAb serum concentrations. Therapeutic drug monitoring (TDM) of mAbs has the potential to guide to more effective dosing in individual patients. This review discusses the mechanisms responsible for interpatient variability of mAb pharmacokinetics, summarizes exposure-response data of mAbs used in inflammatory and malignant disease, presents current evidence of mAb-TDM in inflammatory disease, and provides hurdles and required future steps for further implementing mAb-TDM...
April 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/26164063/-interest-of-biological-documentation-on-brain-metastatic-disease-in-breast-cancer-a-case-report
#15
S Boissonneau, R Faguer, C Joubert, S Fuentes, P Metellus
Breast cancer, after lung cancer, is the second major cause of brain metastases. In breast cancer, the prognosis is closely linked to the molecular subtype of the primary tumor. Targeted therapies, with or without cytotoxic treatment, have significantly modified overall survival in these patients. We report, the case of a patient suffering from breast cancer with brain metastasis in whom the biological documentation of the metastatic disease permitted to tailor the systemic treatment. Analysis of the surgical specimen revealed an immunohistochemical HER2 positive staining, which was not found in the primary tumor and therefore warranted trastuzumab administration...
August 2015: Neuro-Chirurgie
https://www.readbyqxmd.com/read/25661259/clinical-comparison-of-weight-and-age-based-strategy-of-dose-administration-in-children-receiving-intravenous-busulfan-for-hematopoietic-stem-cell-transplantation
#16
COMPARATIVE STUDY
D Gürlek Gökçebay, F Azik, N Ozbek, P Isik, Z Avci, B Tavil, A Kara, B Tunc
Bu, combined with TDM-guided dosing, is associated with fewer graft failures/relapses and lower toxicity in pediatric HSCT. We aimed this retrospective study for comparison of weight- and age-based dosing in terms of clinical outcomes such as time to engraftment, early complications, EFS, OS, and toxicity profiles in children receiving iv Bu. Sixty-one children who underwent HSCT from April 2010 to February 2013 by means of a Bu-based conditioning regimen and completed 100 days after transplantation at Ankara Children?s Hematology and Oncology Hospital Bone Marrow Transplantation Unit were enrolled in this study...
May 2015: Pediatric Transplantation
https://www.readbyqxmd.com/read/25482740/survey-of-antifungal-prophylaxis-and-fungal-diagnostic-tests-employed-in-malignant-haematology-and-haemopoietic-stem-cell-transplantation-hsct-in-australia-and-new-zealand
#17
REVIEW
S J van Hal, N M Gilroy, C O Morrissey, L J Worth, J Szer, C S Tam, S C Chen, K A Thursky, M A Slavin
This article reports the findings of a survey developed to assess the current use of antifungal prophylaxis among haematology and infectious disease clinicians across Australia and New Zealand, and their alignment with existing consensus guidelines for the use of antifungal agents in the haematology/oncology setting (published 2008). Surveyed clinicians largely followed the current recommendations for prophylaxis in the setting of induction chemotherapy for acute myeloid leukaemia, as well as autologous and low-risk allogeneic haemopoietic stem cell transplantation (HSCT)...
December 2014: Internal Medicine Journal
https://www.readbyqxmd.com/read/25336126/-clinical-application-limits-and-perspectives-of-pharmacogenetic-and-pharmacokinetic-analysis-of-anticancer-drugs
#18
REVIEW
Anne-Sophie Chantry, Sylvie Quaranta, Joseph Ciccolini, Bruno Lacarelle
Despite significant progress in the discovery and design of drugs, the interindividual variability to the standard dose of a given drug remains a serious problem in clinical practice. In the future, the aim of pharmacogenetic is to provide new strategies for optimizing drug therapy, both in terms of efficacy and safety. The clinical validation of an increasing number of pharmacogenetic tests, as well as the development of new highly efficient technologies should further promote pharmacogenetics in clinical practice and lead to the optimization and individualization, before treatment, of drug therapy...
September 2014: Annales de Biologie Clinique
https://www.readbyqxmd.com/read/24889915/review-of-therapeutic-drug-monitoring-of-anticancer-drugs-part-1-cytotoxics
#19
REVIEW
Angelo Paci, Gareth Veal, Christophe Bardin, Dominique Levêque, Nicolas Widmer, Jos Beijnen, Alain Astier, Etienne Chatelut
Most anticancer drugs are characterised by a steep dose-response relationship and narrow therapeutic window. Inter-individual pharmacokinetic (PK) variability is often substantial. The most relevant PK parameter for cytotoxic drugs is the area under the plasma concentration versus time curve (AUC). Thus it is somewhat surprising that therapeutic drug monitoring (TDM) is still uncommon for the majority of agents. Goals of the review were to assess the rationale for more widely used TDM of cytotoxics in oncology...
August 2014: European Journal of Cancer
https://www.readbyqxmd.com/read/24878063/therapeutic-drug-monitoring-in-cancer-are-we-missing-a-trick
#20
Christophe Bardin, Gareth Veal, Angelo Paci, Etienne Chatelut, Alain Astier, Dominique Levêque, Nicolas Widmer, Jos Beijnen
Therapeutic drug monitoring (TDM) can be defined as the measurement of drug in biological samples to individualise treatment by adapting drug dose to improve efficacy and/or reduce toxicity. The cytotoxic drugs are characterised by steep dose-response relationships and narrow therapeutic windows. Inter-individual pharmacokinetic (PK) variability is often substantial. There are, however, a multitude of reasons why TDM has never been fully implemented in daily oncology practice. These include difficulties in establishing appropriate concentration target, common use of combination chemotherapies and the paucity of published data from pharmacological trials...
August 2014: European Journal of Cancer
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