Cancer chemotherapy and pharmacology
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Cancer Chemother. Pharmacol. · Jan 2007
Clinical TrialPharmacokinetics and tumor uptake of a derivatized form of paclitaxel associated to a cholesterol-rich nanoemulsion (LDE) in patients with gynecologic cancers.
A cholesterol-rich nanoemulsion termed LDE concentrates in cancer tissues after injection into the bloodstream. The association of a derivatized paclitaxel to LDE showed lower toxicity and increased antitumoral activity as tested in a B16 melanoma murine model. Here, the pharmacokinetics of LDE-paclitaxel oleate and the ability of LDE to concentrate the drug in the tumor were investigated in patients with gynecologic cancers. ⋯ Paclitaxel oleate associated to LDE is stable in the bloodstream and has greater plasma half-life and AUC than those for paclitaxel-cremophor. LDE concentrates 3.5 times more paclitaxel in malignant tissues than in normal tissues. Therefore, association to LDE is an interesting strategy for using paclitaxel to treat gynecologic cancers.
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Cancer Chemother. Pharmacol. · Jan 2007
Comparative StudyA pharmacokinetic and safety study of a novel polymeric paclitaxel formulation for oral application.
To investigate the pharmacokinetics, safety, and tolerability of a new oral formulation of paclitaxel containing the polymer polyvinyl acetate phthalate in patients with advanced solid tumors. ⋯ The AUC of the new polymeric paclitaxel formulation increased a factor 2 in combination with CsA, which confirms that CsA co-administration can also improve exposure to paclitaxel after oral administration of a polymeric formulation. Because of the delayed release of paclitaxel from this formulation, we hypothesize that a split-dose regimen of CsA where it is administered before and after paclitaxel administration will further increase the systemic exposure to paclitaxel up to therapeutic levels. The formulation was well tolerated at the dose of 100 mg without induction of severe toxicities.
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Cancer Chemother. Pharmacol. · Jan 2007
A phase I study of the safety and pharmacokinetics of edotecarin (J-107088), a novel topoisomerase I inhibitor, in patients with advanced solid tumors.
To assess the maximum tolerated dose, safety, and pharmacokinetic (PK) profile of escalating doses of the novel topoisomerase I (topo I) inhibitor edotecarin (J-107088) given as a 2-h intravenous (IV) infusion once every 21 days in patients with advanced solid tumors who had not responded to standard therapy. ⋯ The recommended Phase II dose of edotecarin is 13 mg/m(2) once every 21 days. The toxicities in this study were those typical of cytotoxic chemotherapy and less severe than those associated with other topo I inhibitors. The observed safety profile and preliminary evidence of clinical benefit warrant further investigation of this drug as monotherapy or part of combination therapy in patients with solid tumors.