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Mar. Drugs 2015, 13(1), 379-388; doi:10.3390/md13010379

Combination of Trabectedin and Gemcitabine for Advanced Soft Tissue Sarcomas: Results of a Phase I Dose Escalating Trial of the German Interdisciplinary Sarcoma Group (GISG)

1
University of Heidelberg, Mannheim University Medical Center, Interdisciplinary Tumor Center Mannheim, Sarcoma Unit, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany
2
HELIOS Klinikum Berlin-Buch, Sarcoma Center Berlin-Brandenburg, Schwanebecker Chaussee 50, D-13125 Berlin, Germany
3
HELIOS Klinikum Bad Saarow, Pieskower Straße 33, D-15526 Bad Saarow, Germany
4
University of Heidelberg, Institute of Medical Biometry and Informatics, Im Neuenheimer Feld 305, D-69120 Heidelberg, Germany
*
Author to whom correspondence should be addressed.
Academic Editors: Friedemann Honecker and Sergey Dyshlovoy
Received: 26 November 2014 / Accepted: 24 December 2014 / Published: 13 January 2015
(This article belongs to the Collection Marine Compounds and Cancer)
View Full-Text   |   Download PDF [380 KB, uploaded 24 February 2015]

Abstract

Background: Evaluation of the potential efficacy and safety of combination therapies for advanced soft tissue sarcomas (STS) has increased substantially after approval of trabectedin and pazopanib. Trabectedin's introduction in Europe in 2007 depended mainly on its activity in so-called L-sarcomas (liposarcoma and leiomyosarcoma); combination of trabectedin with other chemotherapies used in STS seems of particular interest. Methods: We initiated within the German Interdisciplinary Sarcoma Group (GISG) a phase I dose escalating trial evaluating the combination of trabectedin and gemcitabine in patients with advanced and/or metastatic L-sarcomas (GISG-02; ClinicalTrials.gov NCT01426633). Patients were treated with increasing doses of trabectedin and gemcitabine. The primary endpoint was to determine the maximum tolerated dose. Results: Five patients were included in the study. Two patients were treated on dose level 1 comprising trabectedin 0.9 mg/m2 on day 1 and gemcitabine 700 mg/m2 on days 1 + 8, every 3 weeks. Due to dose-limiting toxicity (DLT) in both patients (elevated transaminases and thrombocytopenia), an additional three patients were treated on dose level −1 with trabectedin 0.7 mg/m2 plus gemcitabine 700 mg/m2. Of these three patients, two demonstrated another DLT; therefore, the trial was stopped and none of the dose levels could be recommended for phase II testing. Conclusion: The GISG-02 phase I study was stopped with the conclusion that the combination of gemcitabine and trabectedin is generally not recommended for the treatment of patients with advanced and/or metastatic leiomyosarcoma or liposarcoma. Also, this phase I study strongly supports the necessity for careful evaluation of combination therapies. View Full-Text
Keywords: gemcitabine; pazopanib; phase I; safety; soft tissue sarcoma; trabectedin gemcitabine; pazopanib; phase I; safety; soft tissue sarcoma; trabectedin
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. (CC BY 4.0).

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MDPI and ACS Style

Kasper, B.; Reichardt, P.; Pink, D.; Sommer, M.; Mathew, M.; Rauch, G.; Hohenberger, P. Combination of Trabectedin and Gemcitabine for Advanced Soft Tissue Sarcomas: Results of a Phase I Dose Escalating Trial of the German Interdisciplinary Sarcoma Group (GISG). Mar. Drugs 2015, 13, 379-388.

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