Cancer chemotherapy and pharmacology
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Cancer Chemother. Pharmacol. · Jul 2012
Modeling and simulation approaches to evaluate pharmacokinetic sampling contamination from central venous catheters in pediatric pharmacokinetic studies of actinomycin-D: a report from the children's oncology group.
The binding of drugs to catheters can be a source variation in dosing chemotherapeutics. Drug contamination from the dosing central venous line (CVL) can impact the reporting of pharmacokinetic (PK) results and analysis. Peripheral venipuncture avoids binding complications from the CVL but dissuades patients from enrolling. Our group has developed a catheter clearing procedure to minimize the extent of contamination so that dosing and sampling from the CVL can ensue, promoting patient willingness to participate in phase I pediatric oncology trials. ⋯ Drug contamination from sampling catheter can impact AMD PK results and should be accounted for in the analysis. We provide a framework for evaluating catheter contamination and guidance on adjustment in the PK model.
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Cancer Chemother. Pharmacol. · Jul 2012
Multicenter StudyPhase II and gene expression analysis trial of neoadjuvant capecitabine plus irinotecan followed by capecitabine-based chemoradiotherapy for locally advanced rectal cancer: Hoosier Oncology Group GI03-53.
We designed this study in locally advanced rectal cancer to determine the pathological response, toxicity, and disease-free survival (DFS) with induction capecitabine plus irinotecan followed by capecitabine-based chemoradiotherapy (CRT) and analyze the gene expression of enzymes involved in the metabolism of capecitabine and irinotecan for associations with response and toxicity. ⋯ This neoadjuvant regimen was safe and demonstrated significant antitumor activity. High TP tumor gene expression was associated with obtaining pCR.
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Cancer Chemother. Pharmacol. · Jul 2012
The impact of bevacizumab on temozolomide concentrations in intracranial U87 gliomas.
An important question in the sequencing of anti-cancer therapies in patients with glioblastoma (GBM) is whether concurrent anti-angiogenesis therapies improve or impair brain concentrations of concomitantly administered cytotoxic therapies. The purpose of this study is to assess the intratumoral disposition of temozolomide (TMZ) via microdialysis before and after bevacizumab in an intracranial GBM xenograft model. ⋯ There were no statistically significant changes in TMZ pharmacokinetics before or after BEV in the athymic rat U87 intracranial glioma model. BEV and TMZ are being investigated as a combination therapy in several ongoing studies for patients with glioma. These data reassuringly suggest that BEV does not significantly change the ECF tumor concentrations of TMZ in either tumor-bearing or normal brain when dosed 36 h prior to TMZ.