Cancer chemotherapy and pharmacology
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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.