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The Desmoid Tumor Research Foundation

March 2015

Rationale for the use of tyrosine kinase inhibitors in the treatment of paediatric desmoid-type fibromatosis

Author Information

Sparber-Sauer M(1), Orbach D(2), Navid F(3), Hettmer S(4), Skapek S(5,6), Corradini N(7), Casanova M(8), Weiss A(9), Schwab M(10,11), Ferrari A(8).

(1)Klinikum Stuttgart - Olgahospital, Stuttgart Cancer Center, Zentrum fur Kinder-, Jugend- und Frauenmedizin, Pediatrics 5 (Oncology, Hematology, Immunology), Stuttgart, Germany.(2)SIREDO Oncology Center (Care, Innovation and Research for Children, Adolescents & Young Adults with Cancer), PSL Univ, Institut Curie, Paris, France. (3)Dept of Pediatrics, Children's Hospital Los Angeles, Univ of Southern California, Keck School of Medicine, Los Angeles, CA. (4)Dept of Pediatrics & Adolescent Medicine, Division of Pediatric Hematology & Oncology, Faculty of Medicine, University of Freiburg, Freiburg, Germany. (5)Dept of Pediatrics, Univ of Texas Southwestern Medical Center, Dallas, TX. (6)Harold C. Simmons Comprehensive Cancer Center, Univ of Texas Southwestern Medical Center, Dallas, TX. (7)Institut d'Hematologie et d'Oncologie Pediatrique, Centre Leon Berard, Lyon, France. (8)Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy. (9)Dept of Pediatrics, Maine Medical Center, Portland, ME. (10)Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany. (11)Depts of Clinical Pharmacology, Pharmacy, & Biochemistry, University of Tubingen, Tubingen, Germany.

Publication

B JR Cancer

Summary

In children with desmoid-type fibromatosis (DTF) in whom disease progression occurs after an initial watch-and-wait strategy, prolonged low-dose chemotherapy using vinblastine and methotrexate (VBL-MTX) is currently the standard of care. These conventional drugs have been prospectively evaluated but their efficacy and safety profiles are limited, and alternative therapeutic options are therefore essential. Based on the results of clinical trials, the use of tyrosine kinase inhibitors (TKIs) in the treatment of DTF is currently considered only in adult patients. TKIs such as imatinib show superior therapeutic efficacy to VBL-MTX and tolerable short-term side effects for the treatment of adult DFT, supporting the concept of the use of TKIs for the treatment of paediatric DFT. Moreover, new-generation TKIs, such as pazopanib and sorafenib, have shown improved therapeutic efficacy compared to imatinib in adult non-comparative studies. A tolerable safety profile of TKI therapy in children with disease entities other than DTF, such as leukaemia, has been reported. However, the efficacy and, in particular, the long-term safety of TKIs, including childhood-specific aspects such as growth and fertility, for the treatment of children with DTF should be investigated prospectively, as DFT therapy requires long-term drug exposure.

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