Publications by authors named "Julieann Sludden"
Article Synopsis
- The study evaluates 2-OHOA, a synthetic lipid, in a Phase 1/2A trial to determine its safety, tolerability, and efficacy for treating gliomas and advanced solid tumors in 54 patients.
- The trial found that 2-OHOA was well-tolerated at dosage levels, with common side effects being mild gastrointestinal issues, while establishing a recommended phase-2 dose of 12,000 mg daily.
- Some patients, particularly those with high-grade gliomas, showed promising clinical benefits, with 24% experiencing significant positive responses, including one lasting over 2.5 years.
Article Synopsis
- The study focuses on the pharmacokinetics (how the body processes a drug) of cyclophosphamide, an anticancer drug, in infants and young children under two years old, highlighting this often-neglected patient group.
- Analyzed data from 111 samples of 25 patients revealed a wide range of drug clearance rates, showing significant inter-patient variability but no major differences based on age or body weight.
- The findings indicate that while cyclophosphamide clearance for patients under two is similar, it differs notably from older children, suggesting a need for tailored dosing strategies across various tumor types.
Aim: SRA737 is an orally active small-molecule inhibitor of checkpoint kinase 1 being investigated in an oncology setting. A HPLC-MS/MS method for quantifying plasma concentrations of SRA737 was validated.
Methods & Results: Sample preparation involved protein precipitation with acetonitrile following addition of CN-deuterated SRA737 as internal standard.
Article Synopsis
- Life-threatening infections during cancer treatment can limit the effectiveness of cytotoxic therapies, and there is a need for better patient stratification to identify those who may benefit from treatments like colony-stimulation factors.
- A study examined single nucleotide polymorphisms (SNPs) in the CD95 and MBL2 genes, which are related to immune function, to see their links with severe infections after breast cancer treatment with doxorubicin and cyclophosphamide.
- Findings indicated that patients with specific genetic variations (SNPs) had a higher likelihood of experiencing severe infections, highlighting the potential of using pharmacogenetic approaches to predict which individuals may be at greater risk during chemotherapy.
Article Synopsis
- A multi-center phase I study was conducted to evaluate the safety and effectiveness of WX-554, a small molecule inhibitor targeting MEK 1/2, in patients with advanced solid tumors that resisted standard treatments.
- The study followed a dose-escalation approach involving 41 patients, starting with 25 mg weekly and exploring higher doses up to 150 mg weekly and 75 mg twice weekly, without any serious side effects.
- Results showed significant inhibition of ERK phosphorylation and sustained stable disease in a few patients, leading to a recommendation of 75 mg twice weekly as the optimal dose for future trials.
Article Synopsis
- - Rucaparib is a potent oral inhibitor of PARP 1 and 2, showing potential effectiveness in treating advanced breast and ovarian cancers in patients with BRCA-1/2 mutations.
- - A Phase II trial found that although the objective response rate for rucaparib was relatively low (2% for IV and 15% for oral), a significant portion of patients demonstrated stable disease for over 12 weeks and some had responses lasting up to 567 days.
- - The study concluded that rucaparib is well tolerated and requires continuous dosing to achieve the best outcomes, particularly in patients with ovarian cancer.
Introduction: Variation in cyclophosphamide pharmacokinetics and metabolism has been highlighted as a factor that may impact on clinical outcome in various tumour types. The current study in children with B-cell non-Hodgkin's lymphoma (NHL) was designed to corroborate previous findings in a large prospective study incorporating genotype for common polymorphisms known to influence cyclophosphamide pharmacology.
Methods: A total of 644 plasma samples collected over a 5 year period, from 49 B-cell NHL patients ≤ 18 years receiving cyclophosphamide (250 mg/m(2)), were used to characterise a population pharmacokinetic model.
PARP inhibition can enhance the efficacy of temozolomide and prolong survival in orthotopic glioblastoma (GBM) xenografts. The aim of this study was to evaluate the combination of the PARP inhibitor rucaparib with temozolomide and to correlate pharmacokinetic and pharmacodynamic studies with efficacy in patient-derived GBM xenograft models. The combination of rucaparib with temozolomide was highly effective in vitro in short-term explant cultures derived from GBM12, and, similarly, the combination of rucaparib and temozolomide (dosed for 5 days every 28 days for 3 cycles) significantly prolonged the time to tumor regrowth by 40% in heterotopic xenografts.
View Article and Find Full Text PDFObjective: A SNP in the NQO1 gene has been implicated in the response of patients with breast cancer to anthracycline containing regimens. NQO1, and its homologue NQO2, share many substrates yet retain distinct functional differences, with NQO2 being a more permissive molecule for electron accepting substrates. We aimed to determine whether functional NQO2 variants are associated with altered response to adjuvant doxorubicin and cyclophosphamide therapy, with or without tamoxifen, in the treatment of breast cancer.
View Article and Find Full Text PDFPurpose: To assess the safety and tolerability, pharmacokinetics, and early evidence of antitumor activity of escalating doses of MG98, an antisense oligonucleotide to DNA methyltransferase 1 (DNMT1), which has been shown to reduce CpG island methylation and allow reexpression of tumor suppressor genes in vitro.
Experimental Design: In this phase I, open-label study, patients with advanced solid malignancies were treated with escalating doses of MG98 administered as a continuous i.v.
Purpose: To investigate the potential use of accelerator mass spectrometry (AMS) in the study of the clinical pharmacology of imatinib.
Experimental Design: Six patients who were receiving imatinib (400 mg/d) as part of their ongoing treatment for chronic myeloid leukemia (CML) received a dose containing a trace quantity (13.6 kBq) of (14)C-imatinib.
Purpose: To determine the safety, maximum tolerated dose, pharmacokinetics, and toxicities associated with administration of paclitaxel poliglumex (PPX, XYOTAX, Cell Therapeutics, Inc., Bresso, Italy) given on either 3-weekly or 2-weekly schedule.
Experimental Design: Nineteen patients were investigated on the 3-weekly phase Ia study and 11 patients on the 2-weekly phase Ib study.
Determination of anti-cancer drug actinomycin D in human plasma by liquid chromatography-mass spectrometry.
J Chromatogr B Analyt Technol Biomed Life Sci
October 2003
Article Synopsis
- * A sensitive liquid chromatography-mass spectrometry (LC-MS) method was developed to quantify actinomycin D in human plasma, achieving a limit of quantitation of 1.0 ng/ml and demonstrating high reproducibility and accuracy in measurements.
- * The study provides initial insights into the pharmacokinetics of actinomycin D in pediatric patients, which could help optimize treatment and reduce the risk of v