Cancer chemotherapy and pharmacology
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Cancer Chemother. Pharmacol. · Dec 2002
Comparative StudyDosing sequence-dependent pharmacokinetic interaction of oxaliplatin with paclitaxel in the rat.
In a phase I clinical trial of oxaliplatin (OPT) in combination with paclitaxel (PXL), a pharmacokinetic interaction was observed when OPT was given as a 2-h i.v. infusion followed by a 1-h i.v. infusion of PXL. The purpose of this study was to use a rat model to evaluate whether the pharmacokinetic interaction between OPT and PXL is dosing sequence-dependent. ⋯ These results suggest that alterations in the pharmacokinetics of OPT by fPXL are dosing sequence-dependent and mainly caused by the formulation vehicle CrEL. It is suggested that the dosing sequence of fPXL followed by OPT would be more clinically favorable because it would prolong the residence of OPT in systemic circulation. It is further recommended that the use of other formulations of PXL without CrEL or docetaxel would avoid the complication effect of CrEL.
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Cancer Chemother. Pharmacol. · Dec 2002
Comparative StudyAntitumor activity of troxacitabine (Troxatyl) against anthracycline-resistant human xenografts.
We have recently identified a deoxycytidine nucleoside analogue, troxacitabine (beta- L-dioxolane cytidine, Troxatyl; Shire BioChem), which has potent antitumor activity against both leukemia and solid tumors. In contrast to the cytidine nucleoside analogues currently in clinical use (cytarabine and gemcitabine), troxacitabine is a poor substrate of nucleoside transporters and enters cells primarily by passive diffusion. This unusual property led us to evaluate the efficacy of troxacitabine in multidrug resistant (MDR) and multidrug resistance-associated protein (MRP) tumors. ⋯ These results indicate that troxacitabine has a potent in vivo antitumor activity associated with tumor regressions and complete cures in animals with tumors refractory to current chemotherapeutic agents.
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Cancer Chemother. Pharmacol. · Dec 2002
In vitro and in vivo evaluations of the tyrosine kinase inhibitor NSC 680410 against human leukemia and glioblastoma cell lines.
NSC 680410, the novel adamantyl ester of AG957, an inhibitor of the p210bcr/abl tyrosine kinase (CML, Ph(+)) and possibly other kinases, was tested for antitumor activity in ten human leukemia and human glioblastoma cell lines. ⋯ These studies demonstrate that the tyrosine kinase inhibitor NSC 680410 has significant antileukemic activity in p53-null, drug-resistant human leukemia cell lines, as well as significant antitumor activity in combination with Flt-1/Fc chimera against U87 MG glioblastoma brain tumors implanted in situ in athymic mice.
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Cancer Chemother. Pharmacol. · Oct 2002
Comparative StudySuperior effectiveness of ibuprofen compared with other NSAIDs for reducing the survival of human prostate cancer cells.
Although NSAIDs (nonsteroidal antiinflammatory drugs) appear to be effective in the prevention and treatment of prostate cancer, very little information exists on the comparative effects of common nonprescription NSAIDs. In the present investigation, we evaluated the effects of widely used nonprescription NSAIDs on human prostate cancer cells in vitro. ⋯ These observations support the use of ibuprofen in future in vivo studies and in clinical trials designed to test the effectiveness of NSAIDs against human prostate cancer.
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Cancer Chemother. Pharmacol. · Sep 2002
Population pharmacokinetic and limited sampling models for carboplatin administered in high-dose combination regimens with peripheral blood stem cell support.
By means of a nonlinear mixed effect modeling technique, a population pharmacokinetic (PK) model was developed to evaluate the effects of a variety of covariates on clearance and other pharmacokinetic parameters of ultrafilterable carboplatin administered in high-dose combination regimens with peripheral blood stem cell support. In addition, single-sample and two-sample limited sampling models (LSMs) were derived to estimate carboplatin's AUC that could be used in the design of drug dosing regimens. ⋯ Both a population PK model and a LSM for high-dose carboplatin were developed following its administration in combination chemotherapeutic regimens with peripheral blood stem cell support. In both cases, the models performed well when analyzed in the context of the retrospective and bootstrap analyses. Prospective studies in ovarian cancer patients should be conducted to further tailor the current models.