Topotecan clearance based on a single sample and a population pharmacokinetic model: Application to a pediatric high-risk neuroblastoma clinical trial.

Background: Topotecan, an antitumor drug with systemic exposure (SE)-dependent activity against many pediatric tumors has wide interpatient pharmacokinetic variability, making it challenging to attain the desired topotecan SE. The study objectives were to update our topotecan population pharmacokinetic model, to evaluate the feasibility of determining individual topotecan clearance using a single blood sample, and to apply this approach to topotecan data from a neuroblastoma trial to explore exposure-response relationships.

Procedure: Our previous population pharmacokinetic and covariate model was updated using data from 13 clinical pediatric studies.

Disrupted development and integrity of frontal white matter in patients treated for pediatric medulloblastoma.

Background: Treatment of pediatric medulloblastoma is associated with known neurocognitive deficits that we hypothesize are caused by microstructural damage to frontal white matter (WM).

Methods: Longitudinal MRI examinations were collected from baseline (after surgery but before therapy) to 36 months in 146 patients and at 3 time points in 72 controls. Regional analyses of frontal WM volume and diffusion tensor imaging metrics were performed and verified with tract-based spatial statistics.

Pineoblastoma-The Experience at St. Jude Children's Research Hospital.

Background: Pineoblastomas are rare, supratentorial, primitive neuroectodermal tumors.

Objective: To document outcomes with multimodal therapy and evaluate the impact that the degree of surgical resection has on outcome.

Methods: A departmental brain tumor database was queried to identify all patients with pathologically proven pineoblastoma who were treated from January 1997 to June 2015 at St.

Population Pharmacokinetics of Oral Topotecan in Infants and Very Young Children with Brain Tumors Demonstrates a Role of ABCG2 rs4148157 on the Absorption Rate Constant.

For infants and very young children with brain tumors, chemotherapy after surgical resection is the main treatment due to neurologic and neuroendocrine adverse effects from whole brain irradiation. Topotecan, an anticancer drug with antitumor activity against pediatric brain tumors, can be given intravenous or orally. However, high interpatient variability in oral drug bioavailability is common in children less than 3 years old.

Medulloblastoma-translating discoveries from the bench to the bedside.

Medulloblastoma is a form of brain cancer that mainly arises during infancy and childhood. Our understanding of this disease has transitioned rapidly; what was once thought of as a single disease entity is now known to be a compendium comprising at least four distinct subtypes of tumour (Wnt, sonic hedgehog [SHH], group 3, and group 4 medulloblastomas) that have characteristic molecular signatures, distinctive clinical features, and are associated with different outcomes. Importantly, medulloblastomas occurring in infants (aged up to 3 years) and adults have unique characteristics, which distinguish the disease from that seen in children aged >3 years.

Resection of infantile brain tumors after neoadjuvant chemotherapy: the St. Jude experience.

Object: Brain tumors in infants are often large, high grade, and vascular, making complete resection difficult and placing children at risk for neurological complications and excessive blood loss. Neoadjuvant chemotherapy may reduce tumor vascularity and volume, which can facilitate resection. The authors evaluated how an ongoing institutional prospective chemotherapy trial would affect patients who did not have a gross-total resection (GTR) immediately and who therefore required further surgical intervention to achieve definitive tumor resection.

Challenging issues in pediatric oncology.

Improvements in protocol-driven clinical trials and supportive care for children and adolescents with cancer have reduced mortality rates by more than 50% over the past three decades. Overall, the 5-year survival rate for patients with pediatric cancer has increased to approximately 80%. Recognition of the biological heterogeneity within specific subtypes of cancer, the discovery of genetic lesions that drive malignant transformation and cancer progression, and improved understanding of the basis of drug resistance will undoubtedly catalyze further advances in risk-directed treatments and the development of targeted therapies, boosting the cure rates further.

Tyrosine kinase inhibitor enhances the bioavailability of oral irinotecan in pediatric patients with refractory solid tumors.

Purpose: To assess the maximum-tolerated dosages (MTDs), and dose-limiting toxicities (DLTs) of the epidermal growth factor receptor inhibitor gefitinib and of intravenous (IV) irinotecan when administered together in children with refractory solid tumors. To assess the effect of gefitinib on the pharmacokinetics of IV irinotecan and on the bioavailability of a single oral dose of irinotecan.

Patients And Methods: IV irinotecan (15 or 20 mg/m(2)) was given daily for 5 days of 2 consecutive weeks.

Cefixime allows greater dose escalation of oral irinotecan: a phase I study in pediatric patients with refractory solid tumors.

Purpose: Irinotecan is active against a variety of malignancies; however, severe diarrhea limits its usefulness. In our phase I study, the intravenous formulation of irinotecan was administered orally daily for 5 days for 2 consecutive weeks (repeated every 21 days) to children with refractory solid tumors. Our objectives were to determine the maximum-tolerated dose (MTD), dose-limiting toxicity, and pharmacokinetics of oral irinotecan and to evaluate whether coadministration of cefixime (8 mg/kg/d beginning 5 days before irinotecan and continuing throughout the course) ameliorates irinotecan-induced diarrhea.

Phase I and pharmacokinetic study of topotecan administered orally once daily for 5 days for 2 consecutive weeks to pediatric patients with refractory solid tumors.

Purpose: We conducted a phase I trial of the injectable formulation of topotecan given orally once daily for 5 days for 2 consecutive weeks (qd x 5 x 2) in pediatric patients with refractory solid tumors.

Patients And Methods: Cohorts of two to six patients received oral topotecan at 0.8, 1.

Risk factors for traumatic and bloody lumbar puncture in children with acute lymphoblastic leukemia.

Context: Traumatic or bloody lumbar puncture (LP) reduces the diagnostic value of the procedure and may worsen the outcome of patients with acute lymphoblastic leukemia (ALL). Little is known about the risk factors for traumatic and bloody LP.

Objectives: To determine the risk factors for traumatic and bloody LP.