Garcia-Carbonero, R., Supko, J. G., Manola, J., Seiden, M. V., Harmon, D., Ryan, D. P., Quigley, M. T., Merriam, P., Canniff, J., Goss, G., Matulonis, U., Maki, R. G., Lopez, T., Puchalski, T. A., Sancho, M. A., Gomez, J., Guzman, C., Jimeno, J., Demetri, G. D. (April 2004) Phase II and pharmacokinetic study of ecteinascidin 743 in patients with progressive sarcomas of soft tissues refractory to chemotherapy. J Clin Oncol, 22 (8). pp. 1480-90. ISSN 0732-183X (Print)0732-183X (Linking)
Abstract
PURPOSE: To assess the efficacy of the marine-derived alkaloid ecteinascidin 743 (ET-743) in patients with soft tissue sarcomas that progressed despite prior conventional chemotherapy and to characterize the pharmacokinetic profiles of ET-743 in this patient population. PATIENTS AND METHODS: Thirty-six previously treated soft tissue sarcoma patients from three institutions received ET-743 as a 24-hour continuous intravenous (IV) infusion at a dose of 1,500 microg/m(2) every 3 weeks. Pharmacokinetic studies were also performed. Patients were restaged every two cycles for response by objective criteria. RESULTS: Objective responses were observed in three patients, with one complete response and two partial responses, for an overall response rate of 8% (95% CI, 2% to 23%). Responses were durable for up to 20 months. Two minor responses (43% and 47% tumor reduction) were observed, for an overall clinical benefit rate of 14%. The predominant toxicities were neutropenia and self-limited transaminitis of grade 3 to 4 severity in 34% and 26% of patients, respectively. The estimated 1-year time to progression and overall survival rates were 9% (95% CI, 3% to 27%) and 53% (95% CI, 39% to 73%), respectively. The maximum observed plasma concentration and total plasma clearance of ET-743 (mean +/- standard deviation), 1.04 +/- 0.48 ng/mL and 35.6 +/- 16.2 L/h/m(2), respectively, were consistent with previously reported values from phase I studies of the drug given as a 24-hour IV infusion. CONCLUSION: ET-743 is a promising new option for the management of several histologic subtypes of sarcoma. Durable objective responses were obtained in a subset of sarcoma patients with disease progression despite prior chemotherapy. Additionally, the relatively high survival rate noted in this series of previously treated patients further justifies development of this agent.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Adult Antineoplastic Agents, Alkylating/pharmacokinetics/*therapeutic use Dioxoles/adverse effects/pharmacokinetics/*therapeutic use Disease Progression Disease-Free Survival Drug Administration Schedule Drug Resistance, Neoplasm Female Humans Isoquinolines/adverse effects/pharmacokinetics/*therapeutic use Male Middle Aged Neoplasm Metastasis Sarcoma/*drug therapy Soft Tissue Neoplasms/*drug therapy Survival Rate Tetrahydroisoquinolines |
| Subjects: | diseases & disorders > cancer > drugs and therapies > chemotherapy diseases & disorders > cancer > drugs and therapies diseases & disorders > cancer > cancer types > sarcoma |
| CSHL Authors: | |
| Communities: | CSHL labs > Maki lab |
| Depositing User: | Matt Covey |
| Date: | 15 April 2004 |
| Date Deposited: | 26 Oct 2016 20:52 |
| Last Modified: | 26 Oct 2016 20:52 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/33653 |
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