scholarly journals Perspectives and Expertise in Establishing a Therapeutic Drug Monitoring Programme for Challenging Childhood Cancer Patient Populations

2022 ◽  
Vol 11 ◽  
Author(s):  
Shelby Barnett ◽  
Victoria Holden ◽  
Quentin Campbell-Hewson ◽  
Gareth J. Veal

The utility of Therapeutic Drug Monitoring (TDM) in the setting of childhood cancer is a largely underused tool, despite the common use of cytotoxic chemotherapeutics. While it is encouraging that modern advances in chemotherapy have transformed outcomes for children diagnosed with cancer, this has come at the cost of an elevated risk of life-changing long-term morbidity and late effects. This concern can limit the intensity at which these drugs are used. Widely used chemotherapeutics exhibit marked inter-patient variability in drug exposures following standard dosing, with fine margins between exposures resulting in toxicity and those resulting in potentially suboptimal efficacy, thereby fulfilling criteria widely accepted as fundamental for TDM approaches. Over the past decade in the UK, the paediatric oncology community has increasingly embraced the potential benefits of utilising TDM for particularly challenging patient groups, including infants, anephric patients and those receiving high dose chemotherapy. This has been driven by a desire from paediatric oncologists to have access to clinical pharmacology information to support dosing decisions being made. This provides the potential to modify doses between treatment cycles based on a comprehensive set of clinical information, with individual patient drug exposures being used alongside clinical response and tolerability data to inform dosing for subsequent cycles. The current article provides an overview of recent experiences of conducting TDM in a childhood cancer setting, from the perspectives of the clinicians, scientists and pharmacists implementing TDM-based dosing recommendations. The ongoing programme of work has facilitated investigations into the validity of current approaches to dosing for some of the most challenging childhood cancer patient groups, with TDM approaches now being expanded from well-established cytotoxic drugs through to newer targeted treatments.

2001 ◽  
Vol 23 (6) ◽  
pp. 650-657 ◽  
Author(s):  
Alwin D. R. Huitema ◽  
Ron A. A. Mathôt ◽  
Matthijs M. Tibben ◽  
Sjoerd Rodenhuis ◽  
Jos H. Beijnen

2018 ◽  
Vol 85 (1) ◽  
pp. 266-269 ◽  
Author(s):  
Pier Giorgio Cojutti ◽  
Maria Merelli ◽  
Lorenzo Allegri ◽  
Giuseppe Damante ◽  
Matteo Bassetti ◽  
...  

2001 ◽  
Vol 47 (8) ◽  
pp. 1437-1442 ◽  
Author(s):  
Thomas E Mürdter ◽  
Janet Coller ◽  
Alexander Claviez ◽  
Frank Schönberger ◽  
Ute Hofmann ◽  
...  

Abstract Background: High-dose busulfan is widely used in conditioning regimens before hematopoietic stem cell transplantation in both adults and children. Large interindividual variability in pharmacokinetics after oral administration has been reported; therefore, therapeutic drug monitoring of busulfan may decrease the incidence of drug-related toxicity (for example, hepatic venoocclusive disease) and may also improve therapeutic efficacy. Methods: Busulfan concentrations were quantified using 200 μL of plasma and liquid–liquid extraction with diethyl ether after the addition of [2H8]busulfan as the internal standard. Separation and detection of busulfan and [2H8]busulfan were achieved with a LUNA C8 column (5 μm; 150 × 2 mm i.d.) at 30 °C, a HP 1100 liquid chromatography system, and a HP 1100 single-quadrupole mass spectrometer. Busulfan and [2H8]busulfan were detected as ammonium adducts in selected-ion monitoring mode at m/z 264.2 and 272.2, respectively. Results: The calibration curve was linear at 5–2000 μg/L busulfan. Intra- and interassay imprecision (CV) and bias were both <11%. The limits of detection and quantification were 2 and 5 μg/L, respectively. Extraction recovery of busulfan was >87%. Analysis of pharmacokinetics in four patients receiving high-dose busulfan indicated that minimum busulfan concentrations before the next dose were 405–603 μg/L, with no interference observed. Conclusions: The new rapid and sensitive liquid chromatographic–mass spectrometric assay is an appropriate method for quantification of busulfan in human plasma, making therapeutic drug monitoring of busulfan faster and easier in clinical practice.


2015 ◽  
Vol 47 (10) ◽  
pp. 739-742 ◽  
Author(s):  
Menino Osbert Cotta ◽  
Belinda Gowen ◽  
Natasha Truloff ◽  
Evan Bursle ◽  
Brett McWhinney ◽  
...  

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1150-1150
Author(s):  
Zuzana Hassan ◽  
Marie Sandström ◽  
Moustapha Hassan

Abstract Busulphan (Bu) is used in high dose conditioning regimen prior to stem cell transplantation. Bu has a narrow therapeutic window and over- and under-dosing may have a fatal outcome. Bu pharmacokinetics and pharmacodynamics were extensively studied and wide inter- and intra-individual variation was found. Several limited sampling models (LSM) have been developed for Bu administered orally to simplify therapeutic drug monitoring and consequently dose adjustment. The aim of this study was to evaluate the existing LSM in adults and children undergoing conditioning regimen before SCT. Seventy-four patients (62 adults and 12 children) with malignant and non-malignant diseases were analysed. Plasma was sampled at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5 and 6 hours after the first dose of Bu. Bu was determined using gas chromatography with electron capture detection. The area under the plasma concentration-time curve (AUC) for time interval 0 to 6 hours was determined using Winnonlin program and trapezoidal rule. Results were compared to the estimated AUCs using LSMs (Vassal 1992, Schuler 1994, Hassan 1996, Chatergoon 1997). The best correlation between the AUCs determined using trapezoidal rule and 3-points model by Schuler was found (R²=0.95 for all patients, R²=0.97 for children and R²=0.94 for adults). In children, a correlation between AUCs determined with trapezoidal rule and following LSMs was found: 2-points LSM by Schuler (R²=0.94), LSM by Hassan (R²=0.94), LSM by Vassal (R²=0.81) and 3 of 5 LSMs by Chatergoon (R²=0.85, 0.88 and 0.87, resp.). AUCs in children determined using Winnonlin showed good correlation with both Schuler’s models, model by Hassan and one of 4-points models by Chatergoon. However, the correlation between the AUCs determined using trapezoidal rule and Winnonlin was good in children (R²=0.98), but not in adults (R²=0.65). Thus, several limited sampling models are suitable for AUC estimation in children, while there is only one suitable model for adults. This conclusion is made with reservation that even the trapezoidal rule may underestimate the real AUC dependent on sampling density.


Author(s):  
Guangyu Shao ◽  
Bakari Chitechi ◽  
Gamze Demireli ◽  
Karoline Ornig ◽  
Matthias J. Neuböck ◽  
...  

Summary Background Gastrointestinal tuberculosis (TB) is a rare manifestation in low TB-incidence countries such as Austria. It is usually seen in immunocompromised patients or in migrants being more susceptible for extrapulmonary disease manifestations. Case description We report a very rare manifestation of severe gastrointestinal TB in a 49-year-old previously healthy man from Upper Austria. Endoscopy showed a large tumor mass obstructing about 2/3 of the lumen of the cecum. Positron emission tomography/computed tomography scan revealed not only a high metabolic activity in the tumor mass, but also active pulmonary lesions in both upper lung lobes. Bronchial secretion showed acid-fast bacilli in the microscopy and polymerase chain reaction was positive for M. tuberculosis complex. Phenotypic resistance testing showed no resistance for first-line anti-TB drugs. Treatment with isoniazid, rifampicin, pyrazinamide and ethambutol was initiated. Based on therapeutic drug monitoring, the standard treatment regime was adapted to rifampicin high dose. TB treatment was well tolerated and the patient achieved relapse-free cure one year after the end of treatment. Conclusion Gastrointestinal involvement mimicking an intestinal tumor is a very rare TB manifestation in previously healthy Austrians. However, it should be kept in mind due to increasing migration from countries with higher rates of extrapulmonary TB and due to an increasing number of immunocompromised patients. TB telephone consultations can support medical professionals in the diagnosis and the management of complex TB patients. TB management is currently at a transitional stage from a programmatic to personalized management concept including therapeutic drug monitoring or biomarker-guided treatment duration to achieve relapse-free cure.


2014 ◽  
Vol 6 (4) ◽  
Author(s):  
Sunee Lertsinudom ◽  
Aporanee Chaiyakum ◽  
Supinya Tuntapakul ◽  
Kittisak Sawanyawisuth ◽  
Siriporn Tiamkao ◽  
...  

Epilepsy is a common public health problem and needs multi-disciplinary treatment. Therapeutic drug monitoring (TDM) is one of step of the multi-disciplinary treatment in epilepsy at Epilepsy clinic, Khon Kaen University (Thailand). The TDM service has been established since 2008. Here, we aimed to study the roles of TDM order and epilepsy control. This is a prospective descriptive study in which data collection was done from January 1 to December 31, 2010, the period when pharmacists took part in assessing the appropriateness in measurement and interpretation of TDM in order to provide suggestions for physicians. The 112 patients under study had an average age of 38.21±15.36 years; 254 samples were collected for therapeutic drug monitoring; phenytoin was submitted mostly for drug monitoring at 46.46%; 44.49% of sub-missions for drug level monitoring were made owing to a suspected sub-therapeutic level. Associations were found between reasons of sending samples for drug level monitoring and the measured drug levels, <em>i.e.</em>, 66.67% of drug levels found was so low that they were undetectable in sample for patients’ compliance investigation and 38.94% of the drug levels were found to be sub-therapeutic as for the case where submission of samples was done because of suspected sub-therapeutic level, 40% of the cases were found to be in toxicity range in the cases with suspected over-therapeutic levels and monitoring levels, 58.25% were found to be within the therapeutic range. Pharmacists used the interpreted results in patients’ care by recommending physicians to monitor therapeutic drug closely, to adjust the dosage of drugs, and to recommend checking patients’ compliance in their use of drugs at 56.5, 38.9, and 4.3%, respectively. Physicians’ responses were found to be absolute follow, partial follow and not follow at 77.95, 11.03, and 7.48%, respectively. In conclusion, associations were found between reasons of TDM order and measured drug level. Therapeutic drug monitoring services at the Epilepsy Clinic was useful in supporting clinical information queries. Pharmacists could make use of interpreted drug level information by recommending physicians to monitor drug levels and adjust individual dosage regimen accordingly. It should be noted that physicians accepted pharmacists’ recommendation, denoting multi-disciplinary care team that would lead to greater efficiency.


2017 ◽  
pp. dkw550
Author(s):  
Patrick G. Richards ◽  
Kimberlyn M. Dang ◽  
Carol A. Kauffman ◽  
Kay Lyn Stalker ◽  
David Sudekum ◽  
...  

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