Christodoulou, C V, Ferry, D R, Fyfe, D W, Young, A, Doran, J, Sheehan, T M, Eliopoulos, A, Hale, K, Baumgart, J, Sass, G and Kerr, D J (1998) Phase I trial of weekly scheduling and pharmacokinetics of titanocene dichloride in patients with advanced cancer. Journal of Clinical Oncology, 16 (8). pp. 2761-2769. doi:10.1200/JCO.1998.16.8.2761 ISSN 0732-183X.

Research output not available from this repository.

Request-a-Copy directly from author or use local Library Get it For Me service.

Request Changes to record.

Abstract

Purpose: To determine the maximum-tolerated dose (MTD) and the dose- limiting toxicities (DLTs) of a weekly schedule of titanocene dichloride (TD) and to define the pharmacokinetics of titanium in plasma and urine. Patients and Methods: Twenty patients with a median age of 58 years received 83 courses of TD. TD was given as 1-hour infusion at escalating doses from 70 to 185 mg/m2/wk. Pharmacokinetic analysis was performed in eight patients for total plasma titanium (TPTi) and in three patients for ultrafiltrable titanium (UFTi). Results: At the fifth dose level (185 mg/m2/wk), a variety of DLTs were seen in five patients: fatigue in three, bilirubinemia in one, and hypokalemia in two. A further six patients were treated at 140 mg/m2; only one had dose-limiting creatinine elevation and this dose was therefore defined as the MTD. No myelosuppression or alopecia were observed. One patient with adenocarcinoma of unknown primary had a minor response. Pharmacokinetic analysis showed that TPTi maximum concentration (C(max)) values were linear with dose and elimination of TPTi was triphasic with a long terminal half-life (t 1/4 ; median, 165 hours; range, 89 to 592). Between 7% and 24.3% of the total of administered titanium was eliminated in urine over the first 24 hours. In contrast, UFTi elimination was described by a one-compartment model with a t 1/4 of 0.41 hours; peak levels of UFTi were 5.2% ± 2.5% those of TPTi. Conclusion: The MTD of TD given on a weekly schedule is 140 mg/m2, with cumulative, but reversible creatinine and bilirubin elevation being the DLTs.

Item Type:	Journal Article
Subjects:	R Medicine > R Medicine (General)
Journal or Publication Title:	Journal of Clinical Oncology
ISSN:	0732-183X
Official Date:	1 August 1998
Dates:	Date Event 1 August 1998 Accepted
Volume:	16
Number:	8
Page Range:	pp. 2761-2769
DOI:	10.1200/JCO.1998.16.8.2761
Status:	Not Peer Reviewed
Date of first compliant deposit:	25 July 2018
Date of first compliant Open Access:	31 August 2018

Request changes or add full text files to a record

Repository staff actions (login required)

View Item