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

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.

• Authors: Axel Le Cesne, Sara Cresta, Robert G Maki, Jean Yves Blay, Jaap Verweij, Andrés Poveda, Paolo G Casali, Carme Balaña, Patrick Schöffski, Federica Grosso, Pilar Lardelli, Antonio Nieto, Vicente Alfaro, George D Demetri
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 48 Issue 16 Pg. 3036-44 (Nov 2012) ISSN: 1879-0852 [Electronic] England
• PMID: 22749255 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents, Alkylating
• Dioxoles
• Tetrahydroisoquinolines
• Trabectedin

Topics

• 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
• Trabectedin
• Translocation, Genetic
• Treatment Outcome
• Young Adult