Cancer chemotherapy and pharmacology
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Cancer Chemother. Pharmacol. · Sep 2015
Integrated nonclinical and clinical risk assessment of the investigational proteasome inhibitor ixazomib on the QTc interval in cancer patients.
Ixazomib is the first oral, proteasome inhibitor to reach phase III trials. Here, we present an integrated nonclinical and clinical assessment of ixazomib's effect on QTc intervals. ⋯ Ixazomib has no clinically meaningful effects on QTc or HR. Integrating preclinical data and concentration-QTc modeling of phase 1 data may obviate the need for a dedicated QTc study in oncology. A framework for QT assessment in oncology drug development is proposed.
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Cancer Chemother. Pharmacol. · Aug 2015
Meta AnalysisPopulation pharmacokinetics of kahalalide F in advanced cancer patients.
In this study, we characterize the population pharmacokinetics of kahalalide F (KF), a novel marine anticancer drug, after intravenous (i.v.) administration in advanced cancer patients. ⋯ The integration of pharmacokinetic data from six clinical studies demonstrated KF linear elimination from plasma, dose-proportional exposure and time-independent pharmacokinetics. Based on analyzed data, no clinically relevant covariates were identified as predictors of KF pharmacokinetics.
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Cancer Chemother. Pharmacol. · Aug 2015
Phase I study of non-pegylated liposomal doxorubicin in children with recurrent/refractory high-grade glioma.
To determine the maximum recommended dose (RD) and pharmacokinetics of Myocet®, a non-pegylated liposomal doxorubicin, in children. ⋯ The RD of Myocet® administered every 3 weeks to paediatric patients was 60 mg/m(2). The efficacy of Myocet® in paediatric patients with high-grade glioma remains to be determined and should be studied in Phase II trials.
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Cancer Chemother. Pharmacol. · Jul 2015
Multicenter Study Clinical TrialInitial safety report on the tolerability of modified FOLFOX6 as adjuvant therapy in patients with curatively resected stage II or III colon cancer (JFMC41-1001-C2: JOIN trial).
Adjuvant FOLFOX is a widely accepted standard therapy for resected colon cancer. The incidence of grade 3-4 peripheral sensory neuropathy (PSN) was 12.4 and 5.7 % in the MOSAIC and Eastern MASCOT trials, while that of grade 3-4 allergic reactions (AR) was 2.9 and 3.1 %, respectively. The JFMC41-1001-C2 trial (JOIN trial) investigated the tolerability of modified FOLFOX6 (mFOLFOX6) in Japanese colon cancer patients. ⋯ Adjuvant mFOLFOX6 is tolerable for Japanese patients with colon cancer.
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Cancer Chemother. Pharmacol. · May 2015
Vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) rechallenge for patients with metastatic renal cell carcinoma after treatment failure using both VEGFR-TKI and mTOR inhibitor.
To assess the efficacy of vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) rechallenge for metastatic renal cell carcinoma (mRCC) patients and to identify predictive factors for increased progression-free survival (PFS) or overall survival (OS). ⋯ VEGFR-TKI rechallenge may be a viable option for select metastatic RCC patients who fail both VEGFR-TKI and mTORi therapies.