Cancer chemotherapy and pharmacology
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Cancer Chemother. Pharmacol. · Jan 2012
Randomized Controlled TrialA phase I ascending single-dose study of the safety, tolerability, and pharmacokinetics of bosutinib (SKI-606) in healthy adult subjects.
Bosutinib (SKI-606), a dual Src/Abl tyrosine kinase inhibitor, is in clinical development for the treatment of patients with chronic myelogenous leukemia (CML). To support clinical development, we conducted a dose-escalation and food-effect evaluation of safety, tolerability, and pharmacokinetics (PK) of bosutinib in healthy adults. ⋯ Bosutinib 200-600 mg with food was safe and well tolerated. Under fed conditions, bosutinib exposures were linear and dose proportional, and C (max) increased by ~1.5-fold. The t (1/2) supported a once-daily dosing regimen.
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Cancer Chemother. Pharmacol. · Jan 2012
Meta Analysis Comparative StudyMeta-analysis of docetaxel-based doublet versus docetaxel alone as second-line treatment for advanced non-small-cell lung cancer.
To compare docetaxel-based doublet with single-agent docetaxel as second-line treatment in non-small-cell lung cancer (NSCLC). ⋯ This was the first meta-analysis of docetaxel-based doublet versus single-agent docetaxel as second-line therapy in the treatment of non-small-cell lung cancer. The results indicated that docetaxel-based doublet therapy did not gain any benefit in survival but significantly improved PFS and better ORR versus single-agent docetaxel. However, more incidences of grade 3 or 4 neutropenia, thrombocytopenia, and diarrhea were observed in docetaxel-based doublet group.
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Cancer Chemother. Pharmacol. · Jan 2012
Population pharmacokinetics of PM00104 (Zalypsis(®)) in cancer patients.
The aim of this study was to characterize the population pharmacokinetics of PM00104 (Zalypsis(®)) in cancer patients. ⋯ The integration of phase I pharmacokinetic data demonstrated PM00104 linear elimination from plasma, dose proportionality up to 5,000 μg/m(2), and time-independent pharmacokinetics. No clinically relevant covariates were identified as predictors of PM00104 pharmacokinetics.
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Cancer Chemother. Pharmacol. · Dec 2011
Prevention of cisplatin-induced hearing loss by administration of a thiosulfate-containing gel to the middle ear in a guinea pig model.
Thiosulfate may reduce cisplatin-induced ototoxicity, most likely by relieving oxidative stress and by forming inactive platinum complexes. This study aimed to determine the concentration and protective effect of thiosulfate in the cochlea after application of a thiosulfate-containing high viscosity formulation of sodium hyaluronan (HYA gel) to the middle ear prior to i.v. injection of cisplatin in a guinea pig model. ⋯ HYA gel is an effective vehicle for administration of thiosulfate to the middle ear. Local application of a thiosulfate-containing HYA gel reduces the ototoxicity of cisplatin most likely without compromising its antineoplastic effect. This provides a minimally invasive protective treatment that can easily be repeated if necessary.
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Cancer Chemother. Pharmacol. · Dec 2011
Pharmacokinetic evaluation of the vinorelbine-lapatinib combination in the treatment of breast cancer patients.
The objectives of this study were to investigate the pharmacokinetics of intra-venous vinorelbine combined with lapatinib as well as the effect of covariates in breast cancer patients. ⋯ The pharmacokinetic modeling of vinorelbine and lapatinib was consistent with the results previously reported. BW and platelet count were confirmed as influencing blood CL of vinorelbine. A pharmacokinetic interaction occurred between vinorelbine and lapatinib probably due to lapatinib inhibition of CYP450-3A4. The combined lapatinib administration decreases statistically significant the vinorelbine CL. The maximal tolerated dose for the combination of lapatinib with vinorelbine on a q3w schedule is as follows: lapatinib 1,000 mg/day continuously and vinorelbine 22.5 mg/m(2) D1 & D8.