Trabectedin Followed by Irinotecan Can Stabilize Disease in Advanced Translocation-Positive Sarcomas with Acceptable Toxicity
J. Herzog,
F. von Klot-Heydenfeldt,
S. Jabar,
A. Ranft,
C. Rossig,
U. Dirksen,
J. Van den Brande,
M. D’Incalci,
I. von Luettichau,
P. J. Grohar,
W. E. Berdel,
St. Burdach
Affiliations
J. Herzog
Division of Pediatric Hematology/Oncology, Department of Pediatrics, Comprehensive Cancer Center Munich, Kinderklinik München Schwabing, Klinikum Rechts der Isar, Technische Universität München, München, Germany
F. von Klot-Heydenfeldt
Division of Pediatric Hematology/Oncology, Department of Pediatrics, Comprehensive Cancer Center Munich, Kinderklinik München Schwabing, Klinikum Rechts der Isar, Technische Universität München, München, Germany
S. Jabar
Department of Pediatric Hematology and Oncology, University Children’s Hospital Muenster, Muenster, Germany
A. Ranft
Department of Pediatric Hematology and Oncology, University Children’s Hospital Muenster, Muenster, Germany
C. Rossig
Department of Pediatric Hematology and Oncology, University Children’s Hospital Muenster, Muenster, Germany
U. Dirksen
Department of Pediatric Hematology and Oncology, University Children’s Hospital Muenster, Muenster, Germany
J. Van den Brande
University of Antwerp, Antwerp University Hospital, Wilrijkstraat 10, 2650 Edegem, Belgium
M. D’Incalci
Department of Oncology, Laboratory of Cancer Pharmacology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy
I. von Luettichau
Division of Pediatric Hematology/Oncology, Department of Pediatrics, Comprehensive Cancer Center Munich, Kinderklinik München Schwabing, Klinikum Rechts der Isar, Technische Universität München, München, Germany
P. J. Grohar
Department of Pediatrics, Van Andel Institute, Helen DeVos Children’s Hospital and Michigan State University, Grand Rapids, MI, USA
W. E. Berdel
Department of Medicine A, Hematology and Oncology, University of Muenster, Muenster, Germany
St. Burdach
Division of Pediatric Hematology/Oncology, Department of Pediatrics, Comprehensive Cancer Center Munich, Kinderklinik München Schwabing, Klinikum Rechts der Isar, Technische Universität München, München, Germany
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.
