A5024249524- Acute Lymphoblastic Leukemia research
- Cancer therapeutics and mechanisms
- Neuroblastoma Research and Treatments
- Glioma Diagnosis and Treatment
- HIV/AIDS drug development and treatment
- Cancer Treatment and Pharmacology
- Thyroid Cancer Diagnosis and Treatment
- Lung Cancer Research Studies
- Childhood Cancer Survivors' Quality of Life
- Drug Transport and Resistance Mechanisms
- HIV Research and Treatment
- Brain Metastases and Treatment
- Pharmaceutical studies and practices
- Pharmacological Effects and Toxicity Studies
- Colorectal Cancer Treatments and Studies
- HIV/AIDS Research and Interventions
- Chronic Myeloid Leukemia Treatments
- Pancreatic and Hepatic Oncology Research
- Lung Cancer Treatments and Mutations
- Neuroendocrine Tumor Research Advances
- Retinoids in leukemia and cellular processes
- Cancer, Hypoxia, and Metabolism
- Sarcoma Diagnosis and Treatment
- Neutropenia and Cancer Infections
- Acute Myeloid Leukemia Research
Children's Hospital of Philadelphia
2015-2025
University of Pennsylvania
2013-2025
National Cancer Institute
2006-2023
Center for Cancer Research
2002-2023
St. Jude Children's Research Hospital
2002-2020
Dana-Farber Cancer Institute
2011-2017
University of Colorado Denver
2010-2017
Friends of Cancer Research
2017
Children's Hospital Colorado
2010-2017
United States Food and Drug Administration
2017
To produce concentrations of zidovudine (AZT) in plasma and cerebrospinal fluid that would provide constant inhibition the replication human immunodeficiency virus (HIV), we gave AZT by continuous intravenous infusion to 21 children ranging age from 14 months 12 years who had acquired HIV infection through transfusions or perinatally. All patients were symptomatic before treatment (Class P2 Centers for Disease Control); 13 (62 percent) evidence neurodevelopmental abnormalities. The mean...
The disposition of the synthetic corticosteroids, dexamethasone and prednisolone, in CSF was evaluated following bolus intravenous (IV) intrathecal (IT) injection a nonhuman primate model. Steroid concentration plasma measured with radioimmunoassay celite column chromatography. to ratios prednisolone IV administration were 0.15 +/- 0.02 0.08 0.03, respectively. Although peak levels two steroids reached equally potent when administered systemically equipotent doses, half-life shorter. In...
Preclinical studies have demonstrated that trimetrexate is a potent inhibitor of dihydrofolate reductase from Pneumocystis carinii. On the basis this evidence, lipid-soluble antifolate was used as an antipneumocystis agent in 49 patients with acquired immunodeficiency syndrome (AIDS) and pneumocystis pneumonia. Simultaneous treatment reduced folate leucovorin specific antidote to protect host tissues toxic effects without affecting action trimetrexate. Patients were assigned three groups...
PURPOSE We conducted an open-label, randomized trial to determine whether ICRF-187 would reduce doxorubicin-induced cardiotoxicity in pediatric sarcoma patients. METHODS Thirty-eight patients were receive doxorubicin-containing chemotherapy (given as intravenous bolus) with or without ICRF-187. Resting left ventricular ejection fraction (LVEF) was monitored serially multigated radionuclide angiography (MUGA) scan. The two groups compared for incidence and degree of cardiotoxicity, response...
2′,3′-Dideoxyinosine (ddI) is a dideoxynucleoside with potent activity in vitro against the human immunodeficiency virus (HIV). In initial clinical trials adults, ddI showed evidence of antiretroviral little hematologic toxicity.
<b>Objective: </b> To longitudinally analyze changes in plexiform neurofibroma (PN) volume relation to age and body growth children young adults with neurofibromatosis type 1 inoperable, symptomatic, or progressive PNs, using a sensitive, automated method of volumetric MRI analysis. <b>Methods: We included patients 25 years younger PNs entered natural history study treatment trials who had over ≥16 months. <b>Results: studied 49 (median 8.3 years) 61 median evaluation period 34 months (range...
Journal Article Fluconazole Penetration into Cerebrospinal Fluid: Implications for Treating Fungal Infections of the Central Nervous System Get access Carola A. S. Arndt, Arndt Section Leukemia Biology and Infectious Diseases, Pediatric Branch, National Cancer Institute, Institutes Health, Bethesda, Maryland Search other works by this author on: Oxford Academic PubMed Google Scholar Thomas J. Walsh, Walsh Please address requests reprints to Dr. Building 10, Room 13N240, 20892. Cynthia Lester...
Abstract Acute kidney injury due to high-dose methotrexate (HDMTX) is a serious, life-threatening toxicity that can occur in pediatric and adult patients. Glucarpidase treatment approved by the Food Drug Administration for high concentrations context of dysfunction, but guidelines when use it are unclear. An expert panel was convened provide specific, consensus glucarpidase patients who develop HDMTX-induced nephrotoxicity delayed excretion. The guideline provides recommendations identify...
P-glycoprotein (Pgp) antagonists have been difficult to develop because of complex pharmacokinetic interactions and a failure show meaningful results. Here we report the results pharmacodynamic trial using third-generation, potent, noncompetitive inhibitor Pgp, tariquidar (XR9576), in combination with docetaxel.
To assess the role of recombinant bacterial enzyme, glucarpidase (carboxypeptidase-G(2)), leucovorin, and thymidine in management outcome patients with high-dose methotrexate (HDMTX) -induced nephrotoxicity.Patients HDMTX-induced nephrotoxicity received one to three doses intravenous (IV) leucovorin rescue. The initial cohort (n = 35) also by continuous IV infusion. Subsequently, was restricted prolonged exposure (> 96 hours) (MTX) or substantial MTX toxicity at study entry. Plasma MTX,...
Medullary thyroid carcinoma (MTC) is a manifestation of multiple endocrine neoplasia type 2 (MEN2) syndromes caused by germline, activating mutations in the RET (REarranged during Transfection) proto-oncogene. Vandetanib, VEGF and EGF receptor inhibitor, blocks tyrosine kinase activity active adults with hereditary MTC.We conducted phase I/II trial vandetanib for children (5-12 years) adolescents (13-18 MTC to define recommended dose assess antitumor activity. The starting was 100 mg/m(2)...
Purpose Dasatinib is an orally available tyrosine kinase inhibitor with low nanomolar activity against SRC family kinases, BCR-ABL, c-KIT, EPHA2, and the PDGF-β receptor. was found to have selective in several tumor models Pediatric Preclinical Testing Program. Patients Methods A phase I study of dasatinib pediatric patients refractory solid tumors or imatinib-refractory, Philadelphia chromosome–positive leukemia performed. Dose levels 50, 65, 85, 110 mg/m 2 /dose, administered twice daily...
To determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of sorafenib in children with refractory extracranial solid tumors evaluate tolerability tumor MTD leukemias.Sorafenib was administered orally every 12 hours for consecutive 28-day cycles. Pharmacokinetics (day 1 steady-state) were conducted during cycle 1.Of 65 patients enrolled, 60 eligible. In cohort (n = 49), 4 6 experienced a DLT [hypertension, pain, rash/urticaria,...
RAS is dysregulated in neurofibromatosis type 1 (NF1) related plexiform neurofibromas (PNs). The activity of tipifarnib, which blocks signaling by inhibiting its farnesylation, was tested children and young adults with NF1 progressive PNs.Patients aged 3-25 years NF1-related PNs imaging evidence tumor progression were randomized a double-blinded fashion to receive tipifarnib (200 mg/m(2) orally every 12 h) or placebo (phase A) crossed over the opposite treatment arm at time B). PN volumes...
Abstract Purpose: Anaplastic lymphoma kinase (ALK) aberrations are a promising target for patients with neuroblastoma. We assessed the activity of first-generation ALK inhibitor crizotinib in no known curative treatments and whose tumors harbored an activating alteration. Patients Methods: Twenty relapsed/refractory ALK-positive neuroblastoma received at recommended phase II dose 280 mg/m2/dose. A Simon two-stage design was used to evaluate antitumor monotherapy. Response evaluation occurred...
The receptors for transforming growth factor beta (TGF-beta) and their signaling intermediates make up an important tumor-suppressor pathway. role of one these intermediates--Smad3--in the pathogenesis lymphoid neoplasia is unknown.We measured Smad3 messenger RNA (mRNA) protein in leukemia cells obtained at diagnosis from 19 children with acute leukemia, including 10 T-cell lymphoblastic (ALL), 7 pre-B-cell ALL, 2 nonlymphoblastic (ANLL). All nine exons SMAD3 gene (MADH3) were sequenced....
PURPOSE Recent reports of the dramatic antitumor effect all-trans-retinoic acid (RA) in patients with acute promyelocytic leukemia (APL) have renewed interest oncologic indications for retinoids. Furthermore, a variety pediatric tumors are responsive to RA vitro, which provides additional rationale phase I evaluation children cancer that is refractory standard therapy. PATIENTS AND METHODS A trial administered orally twice daily 28-day treatment courses was performed. Cohorts at least three...
Purpose This pediatric phase I trial of tipifarnib determined the maximum-tolerated dose (MTD), pharmacokinetics, and pharmacodynamics in children with refractory solid tumors neurofibromatosis type 1 (NF1) –related plexiform neurofibromas. Patients Methods Tipifarnib was administered twice daily for 21 days, repeated every 28 days starting at 150 mg/m 2 /dose (n = 4), escalations to 200 12), 275 375 6) /dose. The MTD also evaluated on a chronic continuous dosing schedule 6). Pharmacokinetic...