Cancer chemotherapy and pharmacology
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Cancer Chemother. Pharmacol. · May 2008
Phase-1 trial of gefitinib and temozolomide in patients with malignant glioma: a North American brain tumor consortium study.
This is a phase-I study of gefitinib in combination with temozolomide in patients with gliomas. The goal of the study was to define the maximum tolerated dose (MTD) and to characterize the pharmacokinetics of gefitinib when combined with temozolomide. ⋯ The recommended phase-2 dose of gefitinib when used in combination with temozolomide is 1,000 and 250 mg/day, respectively, for patients on or not on EIAEDs.
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Cancer Chemother. Pharmacol. · Apr 2008
Multicenter StudyA phase-I study evaluating the combination of pegylated liposomal doxorubicin and paclitaxel as salvage chemotherapy in metastatic breast cancer previously treated with anthracycline.
The two main goals of this phase-I study were to determine the maximum-tolerated dose (MTD) and to characterize the toxicity of the combination of pegylated liposomal doxorubicin (PLD; Lipo-Dox) and paclitaxel (PTX) administered on a 3-week schedule in patients with metastatic breast cancer (MBC) who had previously been treated with anthracycline-based therapy. ⋯ The maximal tolerated doses of PLD and PTX are 35 and 160 mg/m2, respectively, administered every 3 weeks. The combination of PLD (30-35 mg/m2) and PTX (150-160 mg/m2) constitutes an active regimen with mild toxicity that merits further study.
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Cancer Chemother. Pharmacol. · Apr 2008
Randomized Controlled TrialAn open-label study to evaluate dose and cycle dependence of the pharmacokinetics of pegylated liposomal doxorubicin.
There are no definitive data in humans on the dose dependence and/or cycle dependence of the pharmacokinetics (PK) of pegylated liposomal doxorubicin (PLD). This study examined the PK of PLD across a twofold dose variation and along 3 cycles. ⋯ While the PK of PLD is not dose-dependent within the dose range of 30-60 mg/m(2), there is evidence of a cycle-dependent effect that results in inhibition of clearance when patients receive successive cycles of PLD. These results suggest the need for dose adjustments of PLD upon retreatment to minimize the risk of toxicity.
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Cancer Chemother. Pharmacol. · Apr 2008
Plasma and cerebrospinal fluid pharmacokinetics of valproic acid after oral administration in non-human primates.
Valproic acid (VPA), a widely used antiepileptic, also inhibits histone deacetylase (HDAC), and is undergoing evaluation as an anti-cancer agent. We studied the pharmacokinetics of VPA in the plasma and cerebrospinal fluid (CSF) in a non-human primate model that is highly predictive of human CSF penetration to determine if levels of VPA required to inhibit HDAC in in vivo models can be attained. ⋯ Valproic acid deserves further study for the treatment of CNS tumors given its high CSF penetration after oral dosing coupled with the anti-tumor activity observed in preclinical studies.
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Cancer Chemother. Pharmacol. · Apr 2008
Proteomic analysis of liver cancer cells treated with suberonylanilide hydroxamic acid.
Suberonylanilide hydroxamic acid (SAHA) is an orally administered histone deacetylase inhibitor (HDACI) that has shown significant antitumor activity in a variety of tumor cells. To evaluate if SAHA has an activity against liver cancer, and with an aim to identify the altered cellular factors upon SAHA treatment, human HepG2 cancer cell line was used as a model, and proteomic approach was utilized to elucidate the molecular mechanisms underlying SAHA's antitumor activity. ⋯ SAHA remarkably inhibited proliferation of HepG2 cancer cells, and induced apoptosis in vitro. Using proteomics approaches, a variety of differentially expressed proteins were identified in HepG2 cancer cells before and after treatment with SAHA. This study will enable a better understanding of the molecular mechanisms underlying SAHA-mediated antitumor effects at the protein level.