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Volume 2016, Article ID 7461783, 6 pages
Clinical Study

Trabectedin Followed by Irinotecan Can Stabilize Disease in Advanced Translocation-Positive Sarcomas with Acceptable Toxicity

1Division of Pediatric Hematology/Oncology, Department of Pediatrics, Comprehensive Cancer Center Munich, Kinderklinik München Schwabing, Klinikum Rechts der Isar, Technische Universität München, München, Germany
2Department of Pediatric Hematology and Oncology, University Children’s Hospital Muenster, Muenster, Germany
3University of Antwerp, Antwerp University Hospital, Wilrijkstraat 10, 2650 Edegem, Belgium
4Department of Oncology, Laboratory of Cancer Pharmacology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy
5Department of Pediatrics, Van Andel Institute, Helen DeVos Children’s Hospital and Michigan State University, Grand Rapids, MI, USA
6Department of Medicine A, Hematology and Oncology, University of Muenster, Muenster, Germany

Received 16 June 2016; Revised 4 September 2016; Accepted 29 September 2016

Academic Editor: R. Lor Randall

Copyright © 2016 J. Herzog et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Background. Preclinical data indicate that trabectedin followed by irinotecan has strong synergistic effects on Ewing sarcoma. This is presumably due to hypersensitization of the tumor cells to the camptothecin as an effect of trabectedin in addition to synergistic suppression of EWS-FLI1 downstream targets. A strong effect was also reported in a human rhabdomyosarcoma xenograft. Procedure. Twelve patients with end-stage refractory translocation-positive sarcomas were treated with trabectedin followed by irinotecan within a compassionate use program. Eight patients had Ewing sarcoma and four patients had other translocation-positive sarcomas. Results. Three-month survival rate was 0.75 after the start of this therapy. One patient achieved a partial response according to RECIST criteria, five had stable disease, and the remaining six progressed through therapy. The majority of patients experienced significant hematological toxicity (grades 3 and 4). Reversible liver toxicity and diarrhea also occurred. Conclusions. Our experience with the combination of trabectedin followed with irinotecan in patients with advanced sarcomas showed promising results in controlling refractory solid tumors. While the hematological toxicity was significant, it was reversible. Quality of life during therapy was maintained. These observations encourage a larger clinical trial.