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Most of oral targeted therapies are tyrosine kinase inhibitors (TKIs). Oral administration generates a complex step in the pharmacokinetics (PK) of these drugs. Inter-individual PK variability is often large and variability observed in response is influenced not only by the genetic heterogeneity of drug targets, but also by the pharmacogenetic background of(More)
BACKGROUND Intravenous (IV) busulfan (Bu) dosing approved in Europe based on 5 body weight (BW) strata has been validated for targeting Bu exposures in children undergoing hematopoietic stem-cell transplantation and with mostly malignant diseases. The authors conducted an observational study aiming to investigate the behavior and ontogeny of IV Bu(More)
OBJECTIVES Vandetanib was approved by the U.S. Food and Drug Association for the treatment of advanced medullary thyroid cancer (MTC). Because body weight (BW) loss is observed in MTC and because low skeletal muscle mass (SM) is associated with drug toxicity, this study assessed effects of vandetanib on SM and adipose tissue (AT) and explored the(More)
AIM This phase II study evaluated efficacy, safety and pharmacokinetics (PK) profile of combination intravenous vinorelbine (VNL) and continuous low doses oral cyclophosphamide (CPM) combination in children and young adults with a recurrent or refractory solid tumour. METHODS A total of 117 patients (median age, 12 years) within six disease strata(More)
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(More)
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(More)
INTRODUCTION Busulfan is widely used in a neuroblastoma setting, with several studies reporting marked inter-patient variability in busulfan pharmacokinetics and pharmacodynamics. The current study reports on the pharmacokinetics of oral versus intravenous (IV) busulfan in high-risk neuroblastoma patients treated on the European HR-NBL-1/SIOPEN study. (More)
BACKGROUND Chronic renal failure is a common pathology. The high frequency of this disease in the general US population has been assessed in the NHANES III study. However, the frequency of chronic renal insufficiency among cancer patients remains unclear. MATERIAL/METHODS 316 cancer patients were in a one-month study, included regardless of their(More)
IMPORTANCE OF THE FIELD The oxazaphosphorines (cyclophosphamide, ifosfamide and trofosfamide) are widely used in clinical practice for their antitumor and immunomodulatory activities. However, their use is associated with toxicities. The metabolism of oxazaphosphorines involves cytochrome P450 biotransformations, leading to highly reactive metabolites such(More)