Phase II and pharmacokinetic study of ecteinascidin 743 in patients with progressive sarcomas of soft tissues refractory to chemotherapy Journal Article
| Authors: | Garcia-Carbonero, R.; Supko, J. G.; Manola, J.; Seiden, M. V.; Hannon, 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. |
| Article Title: | Phase II and pharmacokinetic study of ecteinascidin 743 in patients with progressive sarcomas of soft tissues refractory to chemotherapy |
| 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 μg/m2 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/m2, 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. © 2004 by American Society of Clinical Oncology. |
| Keywords: | adult; cancer chemotherapy; cancer survival; clinical article; controlled study; treatment outcome; disease-free survival; middle aged; survival rate; clinical trial; disease course; neutropenia; cancer growth; side effect; disease free survival; metastasis; controlled clinical trial; phase 2 clinical trial; tumor volume; drug administration schedule; alkylating agent; tumor regression; drug resistance; drug resistance, neoplasm; sarcoma; disease progression; multicenter study; antineoplastic agents, alkylating; neoplasm metastasis; soft tissue sarcoma; drug clearance; drug blood level; drug administration; trabectedin; soft tissue neoplasms; soft tissue tumor; isoquinoline derivative; dioxoles; isoquinolines; transaminitis; tetrahydroisoquinolines; tetrahydroisoquinoline derivative; 1,3 dioxolane derivative; plasma clearance; humans; human; male; female; priority journal; article |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 22 |
| Issue: | 8 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2004-04-15 |
| Start Page: | 1480 |
| End Page: | 1490 |
| Language: | English |
| DOI: | 10.1200/jco.2004.02.098 |
| PROVIDER: | scopus |
| PUBMED: | 15084621 |
| DOI/URL: | |
| Notes: | J. Clin. Oncol. -- Cited By (since 1996):167 -- Export Date: 16 June 2014 -- CODEN: JCOND -- Source: Scopus |
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