Cancer chemotherapy and pharmacology
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Cancer Chemother. Pharmacol. · Dec 2006
Phase I/II trial of biweekly docetaxel and cisplatin with concurrent thoracic radiation for stage III non-small-cell lung cancer.
We conducted phase I and II studies of biweekly docetaxel and cisplatin with concurrent radiotherapy, followed by consolidation chemotherapy with the same drugs in patients with locally advanced, unresectable non-small-cell lung cancer (NSCLC). Our objectives were to define the maximum-tolerated dose and dose-limiting toxicity (DLT) in the phase I study, and to determine the response rate, toxicity, and survival rate at the recommended dose (RD) in the phase II study. ⋯ Biweekly docetaxel and cisplatin with concurrent RT was active and well tolerated in patients with unresectable stage III NSCLC.
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Cancer Chemother. Pharmacol. · Nov 2006
Multicenter StudyA phase I, first in man study of OSI-7836 in patients with advanced refractory solid tumors: IND.147, a study of the Investigational New Drug Program of the National Cancer Institute of Canada Clinical Trials Group.
To determine the maximum tolerated dose (MTD), recommended phase II dose (RP2D), safety, tolerability, toxicity profile, dose-limiting toxicities (DLTs), anti-tumor activity and pharmacokinetics of OSI-7836 given IV on day 1 and day 8 every 3 weeks in patients with advanced incurable cancer. ⋯ OSI-7836 given at 200 mg/m2 on day 1 and day 8 every 3 weekly is associated with manageable toxicity and is recommended for further study. While no objective responses were seen, the significant treatment related lymphopenia suggests that hematologic malignancies may warrant further investigation.
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Cancer Chemother. Pharmacol. · Nov 2006
Comparative Study Clinical TrialEffect of CYP2D6 genetic polymorphism on the population pharmacokinetics of tipifarnib.
Evaluate the effect of CYP2D6 genotype on the pharmacokinetics of tipifarnib. ⋯ These results indicate that CYP2D6 genetic polymorphism does not appreciably influence the pharmacokinetics of tipifarnib. Hence, concomitant administration of potent CYP2D6 inhibitors is anticipated to have little or no significant impact on the systemic exposure to tipifarnib.
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Cancer Chemother. Pharmacol. · Nov 2006
Comparative StudyHigh performance liquid chromatographic analysis and preclinical pharmacokinetics of the heteroarotinoid antitumor agent, SHetA2.
SHetA2 {[(4-nitrophenyl)amino][2,2,4,4-tetramethylthiochroman-6-yl)amino]methane-thione], NSC 726189} is a sulfur-containing heteroarotinoid, which selectively inhibits cancer cell growth and induces apoptosis without activation of nuclear retinoic acid receptors (RARs). The objective was to develop and validate a HPLC/UV method for the determination of SHetA2, and study the pharmacokinetics of SHetA2 in the mouse. ⋯ A highly sensitive HPLC/UV method for the quantification of SHetA2 in plasma has been developed to support pharmacokinetics of SHetA2 in the mouse. Pharmacokinetic behaviors of this drug appear to be favorable for future development.
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Cancer Chemother. Pharmacol. · Sep 2006
Phase I/II study of weekly docetaxel dose escalation in combination with fixed weekly cisplatin and concurrent thoracic radiotherapy in locally advanced non-small cell lung cancer.
We conducted a phase I study to determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLT) of weekly docetaxel and cisplatin (DOC/CDDP) with concurrent thoracic radiotherapy (TRT) in patients with unresectable stage III non-small-cell lung cancer (NSCLC). ⋯ The chemoradiation regimen tested in this study has promising activity and manageable toxicity. The continuous schedule could not be recommended due to excessive toxicity. The main DLT was esophagitis, and it significantly correlated with the plasma AAG concentration.