TY - JOUR
T1 - Efficacy of trabectedin (ecteinascidin-743) in advanced pretreated myxoid liposarcomas
T2 - a retrospective study
AU - Grosso, Federica
AU - Jones, Robin L.
AU - Demetri, George D.
AU - Judson, Ian R.
AU - Blay, Jean Yves
AU - Le Cesne, Axel
AU - Sanfilippo, Roberta
AU - Casieri, Paola
AU - Collini, Paola
AU - Dileo, Palma
AU - Spreafico, Carlo
AU - Stacchiotti, Silvia
AU - Tamborini, Elena
AU - Tercero, Juan Carlos
AU - Jimeno, Josè
AU - D'Incalci, Maurizio
AU - Gronchi, Alessandro
AU - Fletcher, Jonathan A.
AU - Pilotti, Silvana
AU - Casali, Paolo G.
N1 - Funding Information:
FG, RLJ, RS, PCa, PCo, PD, CS, SS, ET, AG, JAF, and SP declared no conflicts of interest. GDD is a consultant for, has an advisory role, has received research funding from, and has paid expert testimony for PharmaMar and Johnson & Johnson; IRJ is a consultant and has an advisory role for PharmaMar; has received honoraria and research funding from PharmaMar; and has paid expert testimony for PharmaMar. JYB, ALC, and PGC are consultants and have advisory roles for PharmaMar, Novartis, and Pfizer, and have received honoraria and research funding from Novartis and Pfizer. JCT and JJ are employed by PharmaMar. JJ owns stocks in Zeltia, PharmaMar's holding corporation. MDI is a consultant for, and has an advisory role for, PharmaMar, and has received research funding from PharmaMar.
PY - 2007/7/1
Y1 - 2007/7/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=34347214071&partnerID=8YFLogxK
U2 - 10.1016/S1470-2045(07)70175-4
DO - 10.1016/S1470-2045(07)70175-4
M3 - Article
C2 - 17586092
AN - SCOPUS:34347214071
SN - 1470-2045
VL - 8
SP - 595
EP - 602
JO - The Lancet Oncology
JF - The Lancet Oncology
IS - 7
ER -