A phase II and pharmacokinetic study of ecteinascidin 743 in patients with gastrointestinal stromal tumors

Ryan, D. P., Puchalski, T., Supko, J. G., Harmon, D., Maki, R., Garcia-Carbonero, R., Kuhlman, C., Winkelman, J., Merriam, P., Quigley, T., Jimeno, J., Manola, J., Demetri, G. D. (2002) A phase II and pharmacokinetic study of ecteinascidin 743 in patients with gastrointestinal stromal tumors. Oncologist, 7 (6). pp. 531-8. ISSN 1083-7159 (Print)1083-7159 (Linking)

URL: https://www.ncbi.nlm.nih.gov/pubmed/12490740
DOI: 10.1634/theoncologist.7-6-531


PURPOSE: To assess the efficacy, tolerability, and pharmacokinetics of ecteinascidin 743 (ET-743) in patients with advanced gastrointestinal stromal tumors (GISTs). PATIENTS AND METHODS: The study was confined to adult patients with radiographically measurable GISTs. ET-743 was administered as a 24-hour continuous i.v. infusion at a dose of 1.5 mg/m(2) repeated every 3 weeks. Pharmacokinetic blood sampling was performed during the first cycle of therapy. Tumors were restaged after every second cycle of therapy. RESULTS: A total of 20 patients was enrolled in the study, 19 of whom were treated with 47 cycles of ET-743 (median 2, range 1-10). Severe toxicities were limited to reversible grade 3 transaminitis in 10 patients and grade 3 fatigue in one patient. There were no objective responses, and disease stabilization occurred in two patients lasting for periods of 4 and 10 months. The 1-year survival rate was 71.1%. Mean +/- standard deviation values of the maximum plasma concentration and total plasma clearance were 1.1 +/- 0.4 ng/ml and 44 +/- 16 l/h/m(2), respectively, for 19 of the 20 patients. CONCLUSION: This study is the first report of a prospective phase II trial to evaluate a cytotoxic agent in patients with GISTs. This study underscores the primary resistance of GISTS to chemotherapy and stands in stark contrast to the encouraging results recently achieved with STI571. The lack of response may be associated with a therapeutically ineffective exposure to the drug based upon the lower incidence of severe toxicities and greater clearance than described in phase I and II trials of ET-743.

Item Type: Paper
Uncontrolled Keywords: Adult Aged Antineoplastic Agents, Alkylating/*pharmacokinetics/*therapeutic use Area Under Curve Dioxoles/*pharmacokinetics/*therapeutic use Dose-Response Relationship, Drug Female Gastrointestinal Neoplasms/*drug therapy Humans Infusions, Intravenous Isoquinolines/*pharmacokinetics/*therapeutic use Male Middle Aged Prospective Studies Survival Analysis Tetrahydroisoquinolines Treatment Outcome
Subjects: diseases & disorders > cancer > drugs and therapies
diseases & disorders > cancer > cancer types > gastrointestinal stromal tumors
CSHL Authors:
Communities: CSHL labs > Maki lab
Depositing User: Matt Covey
Date: 2002
Date Deposited: 26 Oct 2016 21:16
Last Modified: 26 Oct 2016 21:16
Related URLs:
URI: https://repository.cshl.edu/id/eprint/33646

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