Efficacy of trabectedin (ecteinascidin-743) in advanced pretreated myxoid liposarcomas: a retrospective study - 16/08/11
, Robin L Jones, MD b, George D Demetri, MD c, Ian R Judson, ProfMD b, Jean-Yves Blay, ProfMD d, Axel Le Cesne, MD e, Roberta Sanfilippo, MD a, Paola Casieri, PhD f, Paola Collini, MD f, Palma Dileo, MD a, Carlo Spreafico, MD g, Silvia Stacchiotti, MD a, Elena Tamborini, PhD f, Juan Carlos Tercero, PhD h, Josè Jimeno, MD h, Maurizio D’Incalci, MD i, Alessandro Gronchi, MD j, Jonathan A Fletcher, PhD k, Silvana Pilotti, MD f, Paolo G Casali, MD aSummary |
Background |
Previous studies have suggested that trabectedin (ecteinascidin-743) could have antitumour activity in soft-tissue sarcoma. We aimed to study the usefulness of trabectedin in the treatment of patients with myxoid liposarcomas, a subtype of liposarcoma that is associated with specific chromosomal translocations t(12;16)(q13;p11) or t(12;22)(q13;q12) that result in the formation of DDIT3-FUS or DDIT3-EWSR1 fusion proteins.
Methods |
51 patients with advanced pretreated myxoid liposarcoma who started treatment with trabectedin between April 4, 2001, and Sept 18, 2006 at five institutions in a compassionate-use programme were analysed retrospectively. Centralised radiological and pathological reviews were done for most patients. Trabectedin was given either as a 24-h continuous infusion or as a 3-h infusion, every 21 days, at 1·1–1·5 mg2. 558 courses of trabectedin were given in total, with a median of ten courses for each patient (range 1–23). The primary endpoints were response rate and progression-free survival, and the secondary endpoint was overall survival.
Findings |
According to Response Evaluation Criteria in Solid Tumors (RECIST), after a median follow-up of 14·0 months (IQR 8·7–20·0), two patients had complete responses (CR) and 24 patients had partial responses (PR); the overall response was 51% (95% CI 36–65). Five patients had early progressive disease. In 17 of the 23 patients who achieved PR or CR as defined by RECIST and who had centralised radiological review, tissue-density changes, consisting of a decrease in tumour density on CT scan or a decrease in contrast enhancement on MRI (or both), preceded tumour shrinkage. Median progression-free survival was 14·0 months (13·1–21·0), and progression-free survival at 6 months was 88% (79–95).
Interpretation |
Trabectedin was associated with antitumour activity in this series of patients with myxoid liposarcoma. The noted patterns of tumour response were such that tissue density changes occurred before tumour shrinkage in several patients. In some patients, tissue-density changes only were seen. Long-lasting tumour control was noted in responsive patients. The compassionate-use programme is still ongoing. This analysis has resulted in the initiation of two prospective studies to assess the role of trabectedin in the treatment of patients with myxoid liposarcoma in preoperative and metastatic settings. Furthermore, the selective mechanism of action for trabectedin in this translocation-related sarcoma is being studied.
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Vol 8 - N° 7
P. 595-602 - juillet 2007 Retour au numéro
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