Exatecan Mesylate

"目录号: HY-13631A

Exatecan(DX-8951)甲磺酸盐是拓扑异构酶I抑制剂喜树碱的合成类似物，增加了其水溶性和抗肿瘤活性，降低了毒性。

生物活性

Description

Exatecan Mesylate (DX-8951) is a totally synthetic analogue of the topoisomerase I-inhibitor camptothecin, which was synthesised to impart increased aqueous solubility, greater tumour efficacy, and less toxicity than camptothecin itself.IC50 value:Target: topoisomerase IExatecan was given as i.v. infusion over 30 min at a dose of 0.5mg/m2 every day for five consecutive days, repeated every 21 days. Seventy-four percentage of cycles could be given without dose or schedule modification. The main toxicity was haematotoxicity with grade 3/4 neutropenia in 49%, grade 3/4 thrombocytopenia in 23%, and grade 3/4 anaemia in 15% of patients, respectively [1]. The most common drug-related toxicity was neutropenia. Non-hematologic toxicities were mostly mild to moderate; the most common were nausea, vomiting and anorexia. Plasma concentrations of DX-8951 (the anhydrous form of DX-8951f) were well described using a linear 2-compartment PK model. All concentrations and dose events were simultaneously modeled and explained by the population PK model. There was no evidence of non-linearity in the elimination PK, auto-inhibition or induction of DX-8951 clearance over the five days of administration [2]. Thirty-one patients were treated with 100 courses of exatecan at 6 dose-schedule levels. The incidence of the principal dose-limiting toxicities, neutropenia and thrombocytopenia, was unacceptably high at exatecan doses exceeding 0.15 mg/m(2)/day as a 21-day CIVI, which was determined to be the MTD for both MP and HP patients [3].

Clinical Trial

NCT00041236

European Organisation for Research and Treatment of Cancer - EORTC

Sarcoma

May 2002

Phase 2

NCT00045318

Jonsson Comprehensive Cancer Center-National Cancer Institute (NCI)

Unspecified Adult Solid Tumor, Protocol Specific

May 2002

Phase 1

NCT00055939