A retrospective analysis of antitumour activity with trabectedin in translocation-related sarcomas. - Centre de recherche en cancérologie de Lyon (UMR INSERM 1052 ; CNRS 5286 ; Centre Léon Bérard) Accéder directement au contenu
Article Dans Une Revue European Journal of Cancer Année : 2012

A retrospective analysis of antitumour activity with trabectedin in translocation-related sarcomas.

Axel Le Cesne
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Robert G Maki
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Andrés Poveda
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Paolo G Casali
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Carme Balaña
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Patrick Schöffski
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Federica Grosso
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Pilar Lardelli
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Vicente Alfaro
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Résumé

AIMS: Approximately 20% of soft tissue sarcomas (STS) have subtype-specific chromosomal translocations; these generate chimeric oncoproteins which can act as abnormal transcription factors. Since trabectedin can bind to DNA and displace transcription factors, antitumour activity was explored in translocation-related sarcoma (TRS) subtypes. METHODS: The current retrospective pooled analysis includes data from 81 patients with TRS treated in 8 phase II trials. RESULTS: TRS subtypes were: synovial sarcoma (SS, n=45), myxoid-round cell liposarcoma (MRC-L-sarcoma, n=27), alveolar soft part sarcoma (ASPS, n=4), endometrial stromal sarcoma (ESS, n=3) and clear cell sarcoma (CCS, n=2). All but one patient had received prior chemotherapy (median of 2 lines). Patients received a median of 4 trabectedin cycles (range, 1-48; median dose intensity=0.40 mg/m(2)/week). Partial responses according to Response Evaluation Criteria in Solid Tumours (RECIST) occurred in 8 patients (ORR=10%; 95% CI, 4-19%): four in MRC-L-sarcoma; three in SS and one in ESS. Tumour control rate (ORR plus stable disease) was 59% (95% CI, 48-70%). Median PFS was 4.1 months (6-month PFS rate=40%). Median overall survival was 17.4 months (survival rate at 12 months=60%). Trabectedin had a manageable safety profile. CONCLUSION: Trabectedin demonstrates encouraging disease control in TRS. Since these promising results were generally noted in patients following chemotherapy, a phase III randomised trial in first-line is ongoing to compare trabectedin with doxorubicin-based chemotherapy in patients with TRS.

Domaines

Cancer

Dates et versions

hal-01057829 , version 1 (25-08-2014)

Identifiants

Citer

Axel Le Cesne, Sara Cresta, Robert G Maki, Jean Yves Blay, Jaap Verweij, et al.. A retrospective analysis of antitumour activity with trabectedin in translocation-related sarcomas.. European Journal of Cancer, 2012, 48 (16), pp.3036-44. ⟨10.1016/j.ejca.2012.05.012⟩. ⟨hal-01057829⟩
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