Cancer chemotherapy and pharmacology
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Cancer Chemother. Pharmacol. · Jan 2004
Clinical TrialA phase II study of intravenous exatecan mesylate (DX-8951f) administered daily for 5 days every 3 weeks to patients with advanced ovarian, tubal or peritoneal cancer resistant to platinum, taxane and topotecan.
DX-8951f is a water-soluble camptothecin derivative with greater in vivo and in vitro activity than topotecan or irinotecan. The objectives of this phase II study were to determine the antitumor activity, safety and pharmacokinetic profile of DX-8951f administered intravenously for five consecutive days, every 3 weeks in patients with advanced ovarian, tubal and peritoneal cancer resistant to platinum, taxane and topotecan. ⋯ DX-8951f administered parenterally as a single agent daily at a dose of either 0.5 or 0.3 mg/m(2) per day for 5 days is feasible in patients with advanced ovarian, tubal and peritoneal cancer resistant to platinum, taxane and topotecan. Although no responses were observed, a significant number of patients had stable disease with a decrease in CA-125 levels. In this heavily pretreated population, DX-8951f has clinically relevant hematologic and gastrointestinal toxicities in about 25% of patients. DX-8951 appeared to have linear pharmacokinetic characteristics on the basis of multiple administrations.
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Cancer Chemother. Pharmacol. · Jan 2004
Evaluation of the antiangiogenic effect of Taxol in a human epithelial ovarian carcinoma cell line.
Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) are major ligands for the endothelium-specific tyrosine kinase receptor Tie-2 and are important regulators of endothelial cell survival. In the presence of vascular endothelial growth factor (VEGF), vessel destabilization by Ang-2 has been hypothesized to induce an angiogenic response, but in the absence of VEGF, Ang-2 leads to vessel regression. In the present study, a human ovarian cancer cell line was used to investigate the possibility that Taxol might affect the expression of Ang-1, Ang-2, and VEGF. ⋯ Our results show that exposure of ovarian cancer cells to a low concentration of Taxol may inhibit the initiating event in angiogenesis, namely, vascular regression. This information might be valuable in the development of new therapeutic interventions for epithelial ovarian cancer.