Background. Sunitinib inhibits KIT and other members of the split-kinase-domain family of receptor tyrosine kinases. Sunitinib prolongs survival in adult patients with imatinib-resistant gastrointestinal stromal tumor (GIST). We report the experience with sunitinib in pediatric patients with advanced GIST following failure of imatinib. Procedure. Sunitinib therapy was provided through a treatment-use protocol. Patients were 10-17 years old at enrollment. All patients had GIST resistant to imatinib therapy. Sunitinib was administered daily for 4 weeks in 6-week treatment cycles. KIT and platelet-derived growth factor receptor alpha (PDGFRA) genotyping of tumor tissue were performed. Results. One patient achieved a partial response, five patients had stable disease and one patient had progressive disease on sunitinib. The duration of disease stabilization was between 7 and 21+ months, with a mean of 15 months. Time to tumor progression was longer on sunitinib than on prior imatinib treatment for five of six patients. Two patients experienced grade 3 adverse events. All other adverse events were grade 1-2. None of the five patients tested had mutations in KIT or PDGFRA. Conclusion. Sunitinib treatment was associated with substantial initial antitumor activity and acceptable tolerability in this group of pediatric patients with imatinib-resistant GIST.

Sunitinib treatment in pediatric patients with advanced GIST following failure of imatinib / K.A. Janeway, K.H. Albritton, A.D. Van Den Abbeele, G.Z. D'Amato, P. Pedrazzoli, S. Siena, J. Picus, J.E. Butrynski, M. Schlemmer, M.C. Heinrich, G.D. Demetri. - In: PEDIATRIC BLOOD & CANCER. - ISSN 1545-5009. - 52:7(2009), pp. 767-771.

Sunitinib treatment in pediatric patients with advanced GIST following failure of imatinib

S. Siena;
2009

Abstract

Background. Sunitinib inhibits KIT and other members of the split-kinase-domain family of receptor tyrosine kinases. Sunitinib prolongs survival in adult patients with imatinib-resistant gastrointestinal stromal tumor (GIST). We report the experience with sunitinib in pediatric patients with advanced GIST following failure of imatinib. Procedure. Sunitinib therapy was provided through a treatment-use protocol. Patients were 10-17 years old at enrollment. All patients had GIST resistant to imatinib therapy. Sunitinib was administered daily for 4 weeks in 6-week treatment cycles. KIT and platelet-derived growth factor receptor alpha (PDGFRA) genotyping of tumor tissue were performed. Results. One patient achieved a partial response, five patients had stable disease and one patient had progressive disease on sunitinib. The duration of disease stabilization was between 7 and 21+ months, with a mean of 15 months. Time to tumor progression was longer on sunitinib than on prior imatinib treatment for five of six patients. Two patients experienced grade 3 adverse events. All other adverse events were grade 1-2. None of the five patients tested had mutations in KIT or PDGFRA. Conclusion. Sunitinib treatment was associated with substantial initial antitumor activity and acceptable tolerability in this group of pediatric patients with imatinib-resistant GIST.
Clinical trials; Drug resistance; New agents; Pediatric oncology; Soft tissue sarcoma; Adolescent; Antineoplastic Agents; Benzamides; Child; Drug Resistance, Neoplasm; Female; Follow-Up Studies; Gastrointestinal Stromal Tumors; Humans; Imatinib Mesylate; Indoles; Male; Piperazines; Polymerase Chain Reaction; Prognosis; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Proto-Oncogene Proteins c-kit; Pyrimidines; Pyrroles; Receptor, Platelet-Derived Growth Factor alpha; Survival Rate; Treatment Failure; Treatment Outcome; Pediatrics, Perinatology and Child Health; Hematology; Oncology
Settore MED/06 - Oncologia Medica
2009
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/552676
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