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)
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: | https://repository.cshl.edu/id/eprint/33739 |
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