A phase I trial and pharmacokinetic study of sorafenib in children with refractory solid tumors or leukemias: a Children's Oncology Group Phase I Consortium report.

Purpose: To determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of sorafenib in children with refractory extracranial solid tumors and evaluate the tolerability of the solid tumor MTD in children with refractory leukemias.

Experimental Design: Sorafenib was administered orally every 12 hours for consecutive 28-day cycles. Pharmacokinetics (day 1 and steady-state) and pharmacodynamics were conducted during cycle 1.

Circulating endothelial cells and circulating endothelial precursor cells in patients with osteosarcoma.

Background: Circulating endothelial cells (CECs) have been detected at increased numbers in patients with solid cancers. CECs have not been systematically evaluated in patients with osteosarcoma.

Procedure: Patients 12 months to 30 years of age with newly diagnosed high-grade osteosarcoma were eligible for this prospective cohort study.

A multi-centre Canadian pilot study of metronomic temozolomide combined with radiotherapy for newly diagnosed paediatric brainstem glioma.

Purpose: Survival rates for paediatric diffuse intrinsic brainstem glioma (DIBSG) are dismal. Metronomic dosing of temozolomide (TMZ) combined with standard radiotherapy may improve survival by increasing the therapeutic index and anti-angiogenic effect of TMZ. This study aimed to evaluate the safety and efficacy of this regimen in paediatric DIBSG patients.

A Canadian paediatric brain tumour consortium (CPBTC) phase II molecularly targeted study of imatinib in recurrent and refractory paediatric central nervous system tumours.

Purpose: To evaluate the safety, efficacy and pharmacokinetics of imatinib in children with recurrent or refractory central nervous system (CNS) tumours expressing KIT and/or PDGFRA.

Methods: Nineteen patients aged 2-18 years, with recurrent or refractory CNS tumours expressing either of the target receptors KIT and/or PDGFRA (by immunohistochemistry) were eligible. Participants received imatinib orally at a dose of 440 mg/m(2)/day and toxicities and tumour responses were monitored.

In vivo antitumor and antimetastatic activity of sunitinib in preclinical neuroblastoma mouse model.

Neuroblastoma (NB) is one of the most common pediatric solid tumors originating from the neural crest lineage. Despite intensive treatment protocols including megatherapy with hematopoietic stem cell transplantation, the prognosis of NB patients remains poor. More effective therapeutics are required.

Phase I trial and pharmacokinetic study of bevacizumab in pediatric patients with refractory solid tumors: a Children's Oncology Group Study.

Purpose: We conducted a pediatric phase I trial of the vascular endothelial growth factor (VEGF)-neutralizing antibody bevacizumab (BV). Primary aims included estimating the maximum-tolerated dose (MTD) and determining the dose-limiting toxicities (DLTs), pharmacokinetics, and biologic effects of BV in children with cancer.

Patients And Methods: BV (5, 10, 15 mg/kg) was administered intravenously every 2 weeks in 28-day courses to children with refractory solid tumors.

Oral versus high-dose pulse corticosteroids for problematic infantile hemangiomas: a randomized, controlled trial.

Objectives: Oral systemic corticosteroids are the mainstay of treatment for problematic hemangiomas; however, current information is based on anecdotal experience and retrospective studies. We aimed to determine whether systemic steroids are efficacious in proliferating hemangioma and to compare the efficacy and safety of 2 corticosteroid treatment modalities.

Patients And Methods: Twenty patients with problematic hemangiomas of infancy were randomly assigned to either daily oral prednisolone or monthly intravenous pulses of methylprednisolone.

A strategy for controlling potential interactions between natural health products and chemotherapy: a review in pediatric oncology.

The high prevalence of complementary and alternative medicine use including natural health products (NHPs) in the pediatric oncology population is well established. The potential for concurrent use of NHPs with conventional chemotherapy necessitates physician awareness regarding the potential risks and benefits that might come from this coadministration. Knowledge of interactions between NHPs and chemotherapy is poorly characterized; however, an understanding of potential mechanisms of interaction by researchers and clinicians is important.

A pilot pharmacokinetic and antiangiogenic biomarker study of celecoxib and low-dose metronomic vinblastine or cyclophosphamide in pediatric recurrent solid tumors.

Tumor vasculature is a reasonable target for cancer therapy and lower more frequent doses of traditional chemotherapeutics [low-dose metronomic (LDM) chemotherapy] has been shown to have antiangiogenic efficacy. This study evaluated the safety and pharmacokinetics of celecoxib and LDM vinblastine or cyclophosphamide in children with recurrent, refractory solid tumors. We also investigated whether a subset of circulating plasma proteins are surrogate markers of angiogenic activity.

High-Dose celecoxib and metronomic "low-dose" cyclophosphamide is an effective and safe therapy in patients with relapsed and refractory aggressive histology non-Hodgkin's lymphoma.

Purpose: Angiogenesis is increased in aggressive histology non-Hodgkin's lymphoma and may be a target with selective cyclooxygenase-2 inhibition and metronomic chemotherapy.

Experimental Design: We assessed response, toxicity, and biomarkers of angiogenesis to low-dose cyclophosphamide (50 mg p.o.

Metronomic dosing of chemotherapy: applications in pediatric oncology.

Pediatric cancer has a better outcome profile than adult cancers. However, refractory disease and the potential for long-term morbidity resulting from the use of conventional therapies necessitate the development of novel treatments for this population. Recent advances in oncology include the use of low dose metronomic (LDM) chemotherapy.

Inhibition of cyclooxygenase-2 disrupts tumor vascular mural cell recruitment and survival signaling.

Much evidence supports an important role for the inducible enzyme cyclooxygenase-2 (COX-2) in tumor angiogenesis. Previous studies have focused on the role of COX-2 in stimulating endothelial proliferation, with blockade of this enzyme impairing endothelial homeostasis. However, recent data suggest that COX-2 also regulates molecules implicated in endothelial trafficking with pericytes/vascular mural cells (VMC), an interaction crucial to vessel stability.

Targeting cyclooxygenase-2 reduces overt toxicity toward low-dose vinblastine and extends survival of juvenile mice with Friend disease.

Purpose: To test the efficacy of selective therapy against cyclooxygenase-2 in combination with a low-dose regimen of a cytotoxic agent in the treatment of juvenile hematopoietic malignancies in the experimental model, Friend disease.

Experimental Design: Juvenile erythroleukemic mice (n = 8) received no treatment, celecoxib (1600 mg/kg/d), vinblastine (0.5 microg/g twice weekly), vehicle controls, or celecoxib + vinblastine combination (n = 9) over a 6-month period from time of tumor induction.

Celecoxib in human milk: a case report.

Many women of reproductive age take the nonsteroidal antiinflammatory drug celecoxib. No data exist, however, regarding its transfer into human breast milk and safety for breastfed infants. We had the opportunity to obtain such data when a woman who was breastfeeding her infant daughter underwent emergency surgery to remove a gangrenous appendix.

Single-dose and steady-state pharmacokinetics of celecoxib in children.

Background And Objective: Celecoxib is a member of a novel group of agents that selectively inhibit cyclooxygenase 2 (COX-2). COX-2 inhibitors have emerged as an important class of drugs because of the lower incidence of side effects when compared with traditional nonsteroidal anti-inflammatory drugs, which inhibit both cyclooxygenase 1 and COX-2. Because children often differ from adults with respect to drug disposition, the objective of this study was to determine the single-dose and steady-state pharmacokinetics of celecoxib in pediatric patients.