Clinical pharmacokinetics of intravenous treosulfan in patients with advanced solid tumors.
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| Abstract |
Treosulfan (L-threitol- 1,4-bis-methanesulfonate, Ovastat) is a prodrug of a bifunctional alkylating agent with activity in ovarian carcinoma and other solid tumors. For a clinical and pharmacology study, patients with advanced, refractory, or resistant solid tumors were treated with a single-dose intravenous 30-min infusion of 8 or 10 g/m2 treosulfan. A sensitive method for the determination of treosulfan in plasma and urine by reverse-phase high-performance liquid chromatography was developed. A total of 14 plasma and urine treosulfan pharmacokinetics determinations were analyzed in the 8-g/m2 group and 7 were analyzed in the 10-g/m2 group, the maximum tolerated dose for this group of pretreated patients. The terminal half-life of treosulfan was in the range of 1.8 h. AUC and Cmax values were significantly (P < 0.01) higher in the 10-g/m2 group (AUC 708+/-168 versus 977+/-182 microg ml(-1) h, Cmax 465+/-98 versus 597+/-94 microg/ml). The mean urinary excretion of the parent compound was about 25% of the total dose delivered over 48 h (range 5-49%), and about 20% was excreted during the first 6 h after administration. Currently, a clinical phase I pharmacokinetics and dose-escalation trial with autologous blood stem-cell support has been started at 20 g/m2 treosulfan using a 2-h infusion protocol.
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| Authors | R A Hilger, A Harstrick, W Eberhardt, C Oberhoff, M Skorzec, J Baumgart, S Seeber, M E Scheulen |
| Journal | Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 42 Issue 2 Pg. 99-104 ( 1998) ISSN: 0344-5704 [Print] Germany |
| PMID | 9654108 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't) |
| Chemical References |
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