This Article Full Text Full Text (PDF) Erratum (v23,p5276) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Le Cesne, A. Articles by Nielsen, O.S. Search for Related Content PubMed PubMed Citation Articles by Le Cesne, A. Articles by Nielsen, O.S.

Phase II Study of ET-743 in Advanced Soft Tissue Sarcomas: A European Organisation for the Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group Trial

From the Institut Gustave Roussy, Villejuif; Centre Leon Bérard, Lyon; Centre Leclerc, Dijon, France; Royal Marsden Hospital, London; Christie Hospital, Manchester; Weston Park Hospital, Sheffield, UK; U.Z. Gasthuisberg, Leuven; EORTC Data Center, Brussels, Belgium; Rotterdam Cancer Institute, Rotterdam; Antoni van Leuuwenhoekhuis, Amsterdam, the Netherlands; Pharma-Mar, Tres Cantos, Spain; Aarhus University Hospital, Aarhus, Denmark

Address reprint requests to Axel Le Cesne, MD, Department of Medicine, Institut Gustave Roussy, 94805 Villejuif Cedex, France; e-mail: lecesne{at}igr.fr

PURPOSE: This nonrandomized multicenter phase II study was performed to evaluate the activity and safety of Ecteinascidin (ET-743) administered at a dose of 1.5 mg/m² as a 24-hour continuous infusion every 3 weeks in patients with pretreated advanced soft tissue sarcoma.

PATIENTS AND METHODS: Patients with documented progressive advanced soft tissue sarcoma received ET-743 as second- or third-line chemotherapy. Antitumor activity was evaluated every 6 weeks until progression, excessive toxicity, or patient refusal.

RESULTS: One hundred four patients from eight European institutions were included in the study (March 1999 to November 2000). A total of 410 cycles were administered in 99 assessable patients. Toxicity mainly involved reversible grade 3 to 4 asymptomatic elevation of transaminases in 40% of patients, and grade 3 to 4 neutropenia was observed in 52% of patients. There were eight partial responses (PR; objective regression rate, 8%), 45 no change (NC; > 6 months in 26% of patients), and 39 progressive disease. A progression arrest rate (PR + NC) of 56% was observed in leiomyosarcoma and 61% in synovialosarcoma. The median duration of the time to progression was 105 days, and the 6-month progression-free survival was 29%. The median duration of survival was 9.2 months.

CONCLUSION: ET-743 seems to be a promising active agent in advanced soft tissue sarcoma, with no cumulative toxicities. The 6-months progression-free survival observed in advanced soft tissue sarcoma compares favorably with those obtained with other active drugs tested in second-line chemotherapy in previous European Organisation for the Research and Treatment of Cancer trials. The median overall survival was unusually long in these heavily pretreated patients mainly due to the high number of patients who benefit from the drug in terms of tumor control.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

This article has been cited by other articles:

				M. von Mehren, R. J. Schilder, J. D. Cheng, E. Temmer, T. M. Cardoso, F. G. Renshaw, E. Bayever, P. Zannikos, Z. Yuan, and R. B. Cohen A phase I study of the safety and pharmacokinetics of trabectedin in combination with pegylated liposomal doxorubicin in patients with advanced malignancies Ann. Onc., October 1, 2008; 19(10): 1802 - 1809. [Abstract] [Full Text] [PDF]

				I. Ray-Coquard, A. Le Cesne, J. S. Whelan, P. Schoffski, B. N. Bui, J. Verweij, S. Marreaud, M. van Glabbeke, P. Hogendoorn, and J.-Y. Blay A Phase II Study of Gefitinib for Patients with Advanced HER-1 Expressing Synovial Sarcoma Refractory to Doxorubicin-Containing Regimens Oncologist, April 1, 2008; 13(4): 467 - 473. [Abstract] [Full Text] [PDF]

				J. Verweij Other Endpoints in Screening Studies for Soft Tissue Sarcomas Oncologist, April 1, 2008; 13(suppl_2): 27 - 31. [Abstract] [Full Text] [PDF]

				P. G. Casali Clinical Decision-making in Rare Tumors: What Is Needed from Clinical Trials ASCO Educational Book, January 1, 2008; 2008(1): 530 - 533. [Abstract] [Full Text] [PDF]

				M. Tascilar, W. J. Loos, C. Seynaeve, J. Verweij, and S. Sleijfer The Pharmacologic Basis of Ifosfamide Use in Adult Patients with Advanced Soft Tissue Sarcomas Oncologist, November 1, 2007; 12(11): 1351 - 1360. [Abstract] [Full Text] [PDF]

				D. G. Soares, A. E. Escargueil, V. Poindessous, A. Sarasin, A. de Gramont, D. Bonatto, J. A. P. Henriques, and A. K. Larsen From the Cover: Replication and homologous recombination repair regulate DNA double-strand break formation by the antitumor alkylator ecteinascidin 743 PNAS, August 7, 2007; 104(32): 13062 - 13067. [Abstract] [Full Text] [PDF]

				R. G. Maki Gemcitabine and Docetaxel in Metastatic Sarcoma: Past, Present, and Future Oncologist, August 1, 2007; 12(8): 999 - 1006. [Abstract] [Full Text] [PDF]

				A. B. Herrero, C. Martin-Castellanos, E. Marco, F. Gago, and S. Moreno Cross-Talk between Nucleotide Excision and Homologous Recombination DNA Repair Pathways in the Mechanism of Action of Antitumor Trabectedin Cancer Res., August 15, 2006; 66(16): 8155 - 8162. [Abstract] [Full Text] [PDF]

				J. Fayette, I. R. Coquard, L. Alberti, D. Ranchere, H. Boyle, and J.-Y. Blay ET-743: A Novel Agent with Activity in Soft Tissue Sarcomas Oncologist, November 1, 2005; 10(10): 827 - 832. [Abstract] [Full Text] [PDF]

				S. Sleijfer, C. Seynaeve, and J. Verweij Using Single-Agent Therapy in Adult Patients with Advanced Soft Tissue Sarcoma Can Still Be Considered Standard Care Oncologist, November 1, 2005; 10(10): 833 - 841. [Abstract] [Full Text] [PDF]

				J. Verweij Ecteinascidin-743 (ET-743): Early Test or Effective Treatment in Soft Tissue Sarcomas? J. Clin. Oncol., August 20, 2005; 23(24): 5420 - 5423. [Full Text] [PDF]