Pharmacokinetics of Chemotherapeutic Drugs in Pediatric Patients With Down Syndrome and Leukemia

Hefti, Erik; Blanco, Javier G.

doi:10.1097/mph.0000000000000540

Cited by 19 publications

(20 citation statements)

References 39 publications

(43 reference statements)

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“…Altered disposition of specific cytotoxic agents may play a role as well. Pediatric patients with DS displayed higher intracellular thioguanine metabolite concentrations when compared with those without DS . Elevated 42‐hour methotrexate plasma concentrations were observed in subjects with DS .…”

Section: Alterations In Drug Disposition and Drug Responsementioning

confidence: 93%

“…Pediatric patients with DS displayed higher intracellular thioguanine metabolite concentrations when compared with those without DS . Elevated 42‐hour methotrexate plasma concentrations were observed in subjects with DS . Most studies that considered the pharmacokinetics of cytotoxic chemotherapeutic agents in patients with DS postulated that altered cellular environments in the DS setting, rather than pharmacokinetics, drive the differential response to chemotherapy agents .…”

Section: Alterations In Drug Disposition and Drug Responsementioning

confidence: 99%

“…41 Most studies that considered the pharmacokinetics of cytotoxic chemotherapeutic agents in patients with DS postulated that altered cellular environments in the DS setting, rather 216 PHARMACOTHERAPY Volume 37, Number 2, 2017 than pharmacokinetics, drive the differential response to chemotherapy agents. 41 Few large prospective studies have investigated the impact of altered chemotherapy dosing in patients with DS; however, the reports that do exist often recommend treating hematologic malignancies with reduced doses of select cytotoxic chemotherapeutics, combined with close monitoring for toxicity. 16 Pediatric patients with DS and leukemia who received prednisone with L-asparaginase displayed hyperglycemia at a higher rate compared with patients without DS.…”

Section: Hematologic Malignanciesmentioning

confidence: 99%

“…Elevated 42‐hour methotrexate plasma concentrations were observed in subjects with DS . Most studies that considered the pharmacokinetics of cytotoxic chemotherapeutic agents in patients with DS postulated that altered cellular environments in the DS setting, rather than pharmacokinetics, drive the differential response to chemotherapy agents . Few large prospective studies have investigated the impact of altered chemotherapy dosing in patients with DS; however, the reports that do exist often recommend treating hematologic malignancies with reduced doses of select cytotoxic chemotherapeutics, combined with close monitoring for toxicity .…”

Section: Alterations In Drug Disposition and Drug Responsementioning

confidence: 99%

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Pharmacotherapeutic Considerations for Individuals with Down Syndrome

Hefti

Blanco

2017

Pharmacotherapy

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Down syndrome (DS, trisomy 21) is the most common survivable aneuploidy. Individuals with DS may experience multiple comorbid health problems including congenital heart defects, endocrine abnormalities, skin and dental problems, seizure disorders, leukemia, dementia, and obesity. These associated conditions may necessitate pharmacotherapeutic management with various drugs. The complex pathobiology of DS may alter drug disposition and drug response in some cases. For example, reports have documented increased rates of adverse drug reactions in patients with DS treated for leukemia and dementia. Intellectual disability resulting from DS may impact adherence to medication regimens. In this review, we highlight literature focused on pharmacotherapy in DS. We discuss reports of altered drug disposition or response in cases with DS, and explore social factors that may impact medication adherence in the DS setting. Enhanced monitoring during drug therapy in individuals with DS is justified based on reports of altered drug disposition, drug response, and other characteristics present in this population.

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Section: Alterations In Drug Disposition and Drug Responsementioning

confidence: 93%

Section: Alterations In Drug Disposition and Drug Responsementioning

confidence: 99%

Section: Hematologic Malignanciesmentioning

confidence: 99%

Section: Alterations In Drug Disposition and Drug Responsementioning

confidence: 99%

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Pharmacotherapeutic Considerations for Individuals with Down Syndrome

Hefti

Blanco

2017

Pharmacotherapy

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“…The prognosis is favorable when total resection is possible, but in patients not amenable to the eradication, chemotherapy, and/or radiotherapy are the only available therapeutic options. However, these regimes rarely lead to a control of the disease and the prognosis is generally poor (5). Between 60 and 65% of grade 2 and grade 3 PXAs are BRAF p.V600E mutated (6, 7) and treatment with Vemurafenib, a BRAF inhibitor approved for the treatment of BRAF —mutated metastatic melanoma, demonstrated efficacy in several cases of primary brain tumor, including PXAs (8).…”

Section: Introductionmentioning

confidence: 99%

Vemurafenib Treatment of Pleomorphic Xanthoastrocytoma in a Child With Down Syndrome

et al. 2019

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Brain tumors are the most common solid neoplasms of childhood, but they are very rarely reported in children with Down Syndrome (DS), who develop more commonly different types of malignancies. In particular, we hereby report the case of an 8-years-old child with DS that presented to our attention for neurological and endocrinological issues. Brain imaging revealed the presence of a mass that was partially resected revealing a histological diagnosis of Pleomorphic Xanthoastrocytoma (PXA), a rare WHO grade II tumor extending from the diencephalic region into the surrounding brain tissue. These tumors can harbor the BRAF mutation p.V600E, targetable by the specific inhibitor Vemurafenib. After confirming the presence of the mutation in the tumor, the patient was treated with Vemurafenib. The treatment proved to be effective, leading to a partial response and a stabilization of the disease. Usually, in patients with DS a reduction of the dose of chemotherapeutic drugs is necessary. Vemurafenib was instead well-tolerated as the only observed adverse effect was grade I skin toxicity. This is, to our knowledge, the first case of a PXA reported in a child with DS and the first DS patient treated with Vemurafenib.

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