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Sunitinib malate for the treatment of pancreatic neuroendocrine tumors.
TLDR
Continuous daily administration of sunitinib at a dose of 37.5 mg improved progression-free survival, overall survival, and the objective response rate as compared with placebo among patients with advanced pancreatic neuroendocrine tumors.
Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer.
TLDR
Antitumor activity supports further studies in patients with renal cell carcinoma, gastrointestinal, neuroendocrine, and stromal tumors and indicates that potentially active target plasma concentrations > or = 50 ng/mL can be achieved with moderate interpatient variability and a long half-life compatible with a single daily dosing.
Current development of mTOR inhibitors as anticancer agents
TLDR
The clinical development of this drug class is reviewed and future prospects for incorporating these agents into multitarget or multimodality strategies against cancer are looked at.
Phase I pharmacokinetic and pharmacodynamic study of the oral mammalian target of rapamycin inhibitor everolimus in patients with advanced solid tumors.
TLDR
Everolimus was satisfactorily tolerated at dosages up to 70 mg/wk and 10 mg/d with predictable PK and Antitumor activity and PD in tumors require further clinical investigation.
Molecular basis for sunitinib efficacy and future clinical development
TLDR
Key issues for the multitargeted approach in cancer treatment, such as markers of response and development of resistance, and their significance for the future development of sunitinib and other multikinase inhibitors are discussed.
Safety and pharmacokinetics of escalated doses of weekly intravenous infusion of CCI-779, a novel mTOR inhibitor, in patients with cancer.
TLDR
CCI-779 displayed no immunosuppressive effects with manageable and reversible adverse events at doses up to 220 mg/m(2), the highest dose tested and not based on classical definitions of maximum-tolerated dose is being tested in phase II trials in patients with breast and renal cancer.
Metabolism of irinotecan (CPT-11) by CYP3A4 and CYP3A5 in humans.
TLDR
CYP3A plays a major role in the metabolism of CPT-11, with some differences of the metabolic profile exhibited by 3A4 and 3A5, indicating that C PT-11 is preferentially metabolized by CYP3A4.
Phase I safety, pharmacokinetic, and pharmacodynamic trial of ZD1839, a selective oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with five selected solid tumor types.
TLDR
ZD1839 treatment resulted in clinically meaningful disease stabilization across a range of tumor types and doses, and was generally well tolerated, with manageable and reversible AEs at doses up to 600mg/d and dose-limiting toxicity observed at 1,000 mg/d.
mTOR-targeted therapy of cancer with rapamycin derivatives.
TLDR
Evidence suggests that rapamycin derivatives could induce G1-S cell cycle delay and eventually apoptosis depending on inner cellular characteristics of tumour cells, and strategies aimed at detecting human tumours that express BCL-2 and other anti-apoptotic proteins might allow identification of rap Amycin-resistant tumours.
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