Cancer chemotherapy and pharmacology
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Cancer Chemother. Pharmacol. · Jan 2008
Multicenter Study Clinical TrialProspective validation of a novel IV busulfan fixed dosing for paediatric patients to improve therapeutic AUC targeting without drug monitoring.
Oral busulfan clearance is age-dependent and children experience a wide variability in plasma exposure. BSA- or age-based dosing is used with therapeutic drug monitoring (TDM) to reduce this variability. ⋯ No difference in AUC values was observed between weight strata (mean +/- SD 1248 +/- 205 micromol.min), whereas a significant difference in Bu clearance was demonstrated. This new dosing enabled to achieve a mean exposure comparable to that in adults. At dose 1, 91% of patients achieved the targeted AUC range (900-1500 micromol.min) while no patients were underexposed. At doses 9 and 13, over 75% of patients remained within that target whilst most of the others were slightly above. Successful engraftment was achieved in all patients. In conclusion, from infants to adults this new dosing enabled, without TDM and dose adjustment, to successfully target a therapeutic AUC window.
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Cancer Chemother. Pharmacol. · Nov 2007
Comparative StudyNovel biocompatible intraperitoneal drug delivery system increases tolerability and therapeutic efficacy of paclitaxel in a human ovarian cancer xenograft model.
We compared the safety, toxicity, biocompatibility and anti-tumour efficacy of a novel chitosan-egg phosphatidylcholine (ePC) implantable drug delivery system that provides controlled and sustained release of paclitaxel (PTX(ePC)) versus commercial paclitaxel formulated in Cremophor EL (PTX(CrEL)). ⋯ The novel PTX(ePC) formulation is a safer and better tolerated method for PTX administration, with significant increase in MTD and enhanced anti-tumour efficacy, suggesting improved therapeutic index with possible clinical implications in the treatment of ovarian tumours.
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Cancer Chemother. Pharmacol. · Nov 2007
Population pharmacokinetics of a HER2 tyrosine kinase inhibitor CP-724,714 in patients with advanced malignant HER2 positive solid tumors.
To develop a population pharmacokinetic (popPK) model for CP-724,714, a novel HER2 tyrosine kinase inhibitor is under development for the treatment of advanced HER2 positive cancers. ⋯ A popPK model was developed that adequately described the pharmacokinetics of CP-724,714. WT was identified as a covariate on CL/F that reduced ISV and improved model performance. Future studies will further assess the importance of WT as a pharmacokinetic covariate. The proposed popPK model can be used to simulate CP-724,714 Phase 2/3 trials.
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Cancer Chemother. Pharmacol. · Oct 2007
Comparative StudyLocal delivery of temozolomide by biodegradable polymers is superior to oral administration in a rodent glioma model.
Dose-limiting adverse effects of thrombocytopenia and leukopenia prevent augmentation of current temozolomide (TMZ) dosing protocols; therefore, we hypothesized that the direct intracranial delivery of TMZ would lead to improved efficacy in an animal model of malignant glioma in an animal model. ⋯ The survival of tumor-bearing animals was improved with local delivery of TMZ compared with systemic administration. XRT in combination with intracranial TMZ did not cause additional toxicity and prolonged the survival even further.
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Cancer Chemother. Pharmacol. · Sep 2007
Preclinical antitumor activity of the oral platinum analog satraplatin.
Satraplatin is an orally available platinum analog. The purpose of this study was to better characterize satraplatin's preclinical antitumor efficacy in a variety of sensitive and resistant human tumor cell lines and in a prostate cancer xenograft model and to evaluate the effect of satraplatin on PSA expression and/or secretion in a prostate cancer cell line. ⋯ These results demonstrate that satraplatin and JM-118 have preclinical antitumor activity in human prostate cancer and other tumor types as well, including several cell lines displaying drug resistance to cisplatin, docetaxel and mitoxantrone. In addition, the results suggest that PSA should be further evaluated as a relevant marker of clinical response in patients with prostate cancer treated with satraplatin.