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

Le Cesne, A., Cresta, S., Maki, R. G., Blay, J. Y., Verweij, J., Poveda, A., Casali, P. G., Balana, C., Schoffski, P., Grosso, F., Lardelli, P., Nieto, A., Alfaro, V., Demetri, G. D. (November 2012) A retrospective analysis of antitumour activity with trabectedin in translocation-related sarcomas. Eur J Cancer, 48 (16). pp. 3036-44. ISSN 1879-0852 (Electronic)0959-8049 (Linking)

URL: https://www.ncbi.nlm.nih.gov/pubmed/22749255
DOI: 10.1016/j.ejca.2012.05.012

Abstract

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.

Item Type: Paper
Uncontrolled Keywords: Adolescent Adult Aged Antineoplastic Agents, Alkylating/adverse effects/*therapeutic use Clinical Trials, Phase II as Topic Dioxoles/adverse effects/*therapeutic use Disease-Free Survival Female Humans Kaplan-Meier Estimate Male Middle Aged Retrospective Studies Sarcoma/*drug therapy/genetics/mortality/pathology Tetrahydroisoquinolines/adverse effects/*therapeutic use Time Factors *Translocation, Genetic Treatment Outcome Young Adult
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA translocation
diseases & disorders > cancer > drugs and therapies
diseases & disorders > cancer > cancer types > sarcoma
CSHL Authors:
Communities: CSHL labs > Maki lab
Depositing User: Matt Covey
Date: November 2012
Date Deposited: 20 Oct 2016 16:54
Last Modified: 20 Oct 2016 16:54
Related URLs:
URI: http://repository.cshl.edu/id/eprint/33739

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