Phase II, open-label study evaluating the activity of imatinib in treating life-threatening malignancies known to be associated with imatinib-sensitive tyrosine kinases

摘要: Purpose: To evaluate the activity of imatinib in treating advanced, life-threatening malignancies expressing one or more imatinib-sensitive tyrosine kinases. Experimental Design: This was a phase II, open-label, single arm study. Patients ≥15 years old with showing histologic molecular evidence expression/activation kinases were enrolled. treated 400 800 mg/d for hematologic malignancy and solid tumors, respectively. Treatment continued until disease progression unacceptable toxicity. The primary objective to identify tumor response as end point. Results: One hundred eighty-six patients 40 different enrolled (78.5% 21.5% malignancies). Confirmed occurred 8.9% (4 complete, 9 partial) 27.5% (8 3 partial). Notable observed only five types (aggressive fibromatosis, dermatofibrosarcoma protuberans, hypereosinophilic syndrome, myeloproliferative disorders, systemic mastocytosis). A total 106 tumors screened activating mutations: KIT mutations no platelet-derived growth factor receptor found. patient mastocytosis partial therapy had novel mutation (D816T). There clear relationship between expression activation wild-type clinical response. Conclusion: Clinical benefit largely confined diseases known genomic mechanisms target Our results indicate an important role characterization likely from treatment.