Efficacy of trabectedin (ecteinascidin-743) in advanced pretreated myxoid liposarcomas: a retrospective study

Grosso, Federica; Jones, Robin L.; Demetri, George D.; Judson, Ian; Blay, Jean‐Yves; Cesne, Axel Le; Sanfilippo, Roberta; Casieri, Paola; Collini, Paola; Dileo, Palma; Spreafico, Carlo; Stacchiotti, Silvia; Tamborini, Elena; Tercero, Juan Carlos; Jimeno, J.; D’Incalci, Maurizio; Gronchi, Alessandro; Fletcher, Jonathan A.; Pilotti, Silvana; Casali, Paolo G.

doi:10.1016/s1470-2045(07)70175-4

Cited by 420 publications

(298 citation statements)

References 25 publications

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“…10,11 In recent years, however, the insight has emerged that systemic therapy should become more tailored, and particularly for STS, according to histologic subtype. This approach is illustrated clearly by the relevant activity of imatinib in advanced dermatofibrosarcoma protuberans, 12,13 paclitaxel in angiosarcoma, 14,15 gemcitabine in leiomyosarcomas, 16,17 trabectedin in patients with myxoid/round cell liposarcomas, 18 and of mammalian target of rapamycin inhibitors in perivascular epithelioid cell tumors. 19 This evolution has been associated over the last 2 decades with the widespread use of additional lines of chemotherapy along with first-line anthracycline-based regimens; the increasing participation of patients with STS in investigational agents trials; the increased used of locoregional treatments for metastatic disease (surgery, radiofrequency ablation); and the general improvement in oncology supportive care.…”

Section: Discussionmentioning

confidence: 99%

Trends in survival for patients with metastatic soft‐tissue sarcoma

Italiano

Mathoulin‐Pélissier²,

Cesne

et al. 2010

Cancer

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BACKGROUND:The objective of this study was to determine whether the overall survival of patients with metastatic soft tissue sarcoma (STS) has improved over the last 20 years. METHODS: In total, 1024 patients who had synchronous metastatic ( RESULTS:The proportion of patients with SM, the interval between diagnosis and MM, and the clinical characteristics of the patients were similar across the 4 periods. Although there was no significant difference in the median overall survival (OS) from P1 through P2 (P1, 12.3 months; 95% confidence interval [CI], 9.9-14.7 months; P2, 11.4 months; 95% CI, 9-13.9 months), significant improvements were observed in the later periods (P3, 15 months; 95% CI, 11.8-18.2 months; P4, 18 months; 95% CI, 15.3-20.7 months; P ¼ .029; log-rank test). The 2-year OS rate also increased throughout the study period from 28.1% during P1 to 38.7% during P4. On multivariate analysis, period of diagnosis, age, histologic subtype, time to metastatic recurrence, French Federation of Cancer Centers Sarcoma Group grade, and the number of metastatic sites were independent prognostic factors for OS. CONCLUSIONS: The current analysis revealed that the median OS of patients with metastatic STS had improved by 50% during the last 20 years. These data should be considered in the interpretation of results from ongoing and future STS trials.

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Section: Discussionmentioning

confidence: 99%

Trends in survival for patients with metastatic soft‐tissue sarcoma

Italiano

Mathoulin‐Pélissier²,

Cesne

et al. 2010

Cancer

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“…The overall response rate to trabectedin observed in several phase II studies in patients who have failed one or two lines of chemotherapy is around 10%, with disease stabilization exceeding 50%. The more relevant antitumor efficacy is observed in patients with advanced myxoid liposarcoma, in which trabectedin induces objective responses in approximately 50% of cases and progression-free survival exceeding 2 years in 80% of patients (25,26). Myxoid liposarcoma pathogenesis is related to characteristic chromosomal translocations such as t(12;16)(q13;p11) or less frequently t(12;22)(q13;q12), resulting in the expression of FUS-CHOP and EWS-CHOP fusion genes, respectively (27).…”

Section: Mechanism Of Action In Specific Subtypes Of Sarcomasmentioning

confidence: 99%

A Review of Trabectedin (ET-743): A Unique Mechanism of Action

D’Incalci

Galmarini

2010

Molecular Cancer Therapeutics

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Trabectedin (ET-743) is a marine alkaloid isolated from the Caribbean tunicate Ecteinascidia turbinata, with a chemical structure characterized by three fused tetrahydroisoquinoline rings. Two of these rings (subunits A and B) provide the framework for covalent interaction with the minor groove of the DNA double helix, whereas the third ring (subunit C) protrudes from the DNA duplex, apparently allowing interactions with adjacent nuclear proteins. The compound's chemical interactions trigger a cascade of events that interfere with several transcription factors, DNA binding proteins, and DNA repair pathways, likely to be different from other DNA-interacting agents. Trabectedin also causes modulation of the production of cytokines and chemokines by tumor and normal cells, suggesting that the antitumor activity could also be ascribed to changes in the tumor microenvironment. The promising data on the combination of trabectedin with other anticancer agents, observed in preclinical systems, have prompted several clinical studies that are currently ongoing. One of these combinations (trabectedin-pegylated liposomal doxorubicin) was recently authorized by the European Commission for the treatment of patients with relapsed platinum-sensitive ovarian cancer.

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“…22,23 It is noteworthy that pathologic responses without any decrease in size were reported even in patients with solid tumors who received cytotoxic chemotherapy. Patients with myxoid liposarcoma who received trabectedin 24,25 and patients with osteosarcoma who received chemotherapy [26][27][28] are examples among sarcomas. We previously demonstrated that Choi criteria adapted to magnetic resonance imaging (MRI) correlated better with pathologic tumor response than RECIST in a series of 38 patients with high-grade soft tissue sarcomas who received preoperative chemotherapy with or without radiation therapy within a prospective phase 3 Italian Sarcoma Group/Spanish Sarcoma Group trial.…”

Section: Introductionmentioning

confidence: 99%

Tumor response assessment by modified Choi criteria in localized high‐risk soft tissue sarcoma treated with chemotherapy

Stacchiotti

Verderio²,

Messina

et al. 2012

Cancer

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BACKGROUND. The objective of this study was to compare the prognostic relevance of Response Evaluation Criteria in Solid Tumors (RECIST) versus Choi criteria for the assessment of response in patients with high-risk soft tissue sarcoma of the extremities or trunk wall who received preoperative chemotherapy with or without radiotherapy in a phase 3 trial. METHODS. Patients received 3 cycles of preoperative epirubicin þ ifosfamide with or without radiotherapy. The diagnostic concordance between RECIST and Choi criteria and their correlation with overall survival (OS) and freedom from progression (FFP) were evaluated in a univariate Cox regression model. RESULTS. In 243 of 321 eligible patients, RECIST, Choi criteria, and histology were predictive for OS and FFP. In the subgroup of 69 patients who received chemotherapy alone and were evaluable by both RECIST and Choi criteria, Choi criteria were associated significantly with OS and FFP, whereas RECIST predicted only FFP, and the pattern of agreement observed between the 2 criteria was unsatisfactory. On a dichotomous scale, comparing objective response (complete and partial responses) and lack of response (stable and progressive disease) to preoperative chemotherapy according to RECIST and Choi criteria, only Choi criteria were predictive of OS and FFP, and fair agreement between RECIST and Choi criteria was observed. When lack of progression and progression were compared (complete and partial responses þ stable disease vs progressive disease), both assessment criteria were significantly predictive of OS and FFP, and there was substantial agreement between the 2 criteria. CONCLUSIONS. Response to chemotherapy with or without radiotherapy was associated with a better outcome in patients with high-risk soft tissue sarcoma. Choi criteria were better predictors than RECIST in patients who received preoperative chemotherapy alone. Cancer 2012;118:5857-66.

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Efficacy of trabectedin (ecteinascidin-743) in advanced pretreated myxoid liposarcomas: a retrospective study

Cited by 420 publications

References 25 publications

Trends in survival for patients with metastatic soft‐tissue sarcoma

Trends in survival for patients with metastatic soft‐tissue sarcoma

A Review of Trabectedin (ET-743): A Unique Mechanism of Action

Tumor response assessment by modified Choi criteria in localized high‐risk soft tissue sarcoma treated with chemotherapy

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