Jeffrey M. Skolnik

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Inhibition of kinesin spindle protein or Eg5 causes the formation of monoastral mitotic spindles, which leads to cell death. AZD4877 is a specific, potent inhibitor of Eg5. This was a Phase I, open-label, two-part study to evaluate the maximum tolerated dose (MTD) and safety and tolerability of AZD4877 in patients with advanced solid malignancies. In part(More)
PURPOSE To determine the efficacy and safety of pediatric phase I oncology trials in the era of dose-intensive chemotherapy and to analyze how efficiently these trials are conducted. METHODS Phase I pediatric oncology trials published from 1990 to 2004 and their corresponding adult phase I trials were reviewed. Dose escalation schemes using fixed 30% dose(More)
Actinomycin-D is an antineoplastic agent that inhibits RNA synthesis by binding to guanine residues and inhibiting DNA-dependent RNA polymerase. Although actinomycin-D has been used to treat rhabdomyosarcoma and Wilms tumor for more than 40 years, the dose/exposure relationship is not well characterized. The objective of this study was to develop an initial(More)
CONTEXT Current treatment for acute myeloid leukemia (AML) in children cures about half the patients. Of the other half, most succumb to leukemia, but 5% to 15% die of treatment-related complications. Overweight children with AML seem to experience excess life-threatening and fatal toxicity. Nothing is known about how weight affects outcomes in pediatric(More)
PURPOSE To shorten the study conduct timeline of pediatric phase I oncology trials by employing a novel trial design. METHODS A comparison of the traditional 3 + 3 patients per cohort, phase I trial design with a novel, rolling six design was performed by using discrete event simulation. The rolling six design allows for accrual of two to six patients(More)
BACKGROUND Dactinomycin (AMD) and vincristine (VCR) have been used for the treatment of childhood cancer over the past 40 years but evidence-based dosing guidance is lacking. METHODS Patient AMD and VCR dose and drug-related adverse event (AE) information from four rhabdomyosarcoma (RMS) and two Wilms tumor (WT) studies were assembled. Statistical(More)
OBJECTIVES To develop a method for drug dosing and pharmacokinetic (PK) sampling in children with cancer from a single indwelling central venous catheter that minimized drug contamination. METHODS A benchtop system was designed to simulate dosing and clearing actinomycin-D (AMD) and vincristine (VCR) from central venous catheters. The authors evaluated(More)
Tyrosine kinase inhibitors have been used to treat adult cancers for over a decade. Since the discovery of imatinib mesylate (STI-571, Gleevec; Novartis), tyrosine kinase inhibitors have ushered in a new age of targeted therapy. Although the United States Food and Drug Administration has approved several kinase inhibitors for use in adult cancers, currently(More)
The protein expression of the cyclin-dependent kinase inhibitor p27 is often deregulated in human tumors. In lymphomas the inactivation of p27 is achieved through either increased degradation(1) or sequestration via D cyclins,(2) and p27 protein levels have been shown to have a prognostic significance.(1,3) Recently, S-phase kinase-associated protein 2(More)
Seven years after the launch of the European Paediatric Medicine Regulation, limited progress in paediatric oncology drug development remains a major concern amongst stakeholders - academics, industry, regulatory authorities, parents, patients and caregivers. Restricted increases in early phase paediatric oncology trials, legal requirements and regulatory(More)