Nilotinib as Coadjuvant Treatment with Doxorubicin in Patients with Sarcomas: A Phase I Trial of the Spanish Group for Research on Sarcoma
| العنوان: | Nilotinib as Coadjuvant Treatment with Doxorubicin in Patients with Sarcomas: A Phase I Trial of the Spanish Group for Research on Sarcoma |
|---|---|
| المؤلفون: | Alemany R, Moura DS, Redondo A, Martinez-Trufero J, Calabuig S, Saus C, Obrador-Hevia A, Ramos R, Villar VH, Valverde C, Vaz MA, Medina J, Felipe-Abrio I, Hindi N, Taron M, Martin-Broto J |
| المصدر: | CLINICAL CANCER RESEARCH r-FIHGUV. Repositorio Institucional de Producción Científica de la Fundación de Investigación del Hospital General de Valencia instname |
| بيانات النشر: | American Association for Cancer Research, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | body regions |
| الوصف: | Purpose: Nilotinib plus doxorubicin showed to be synergistic regarding apoptosis in several sarcoma cell lines. A phase I/II trial was thus designed to explore the feasibility of nilotinib as coadjuvant of doxorubicin by inhibiting MRP-1/P-gp efflux activity. The phase I part of the study is presented here. Patients and Methods: Nilotinib 400 mg/12 hours was administered in fixed dose from day 1 to 6, and doxorubicin on day 5 of each cycle. Three dose escalation levels for doxorubicin at 60, 65, and 75 mg/m(2) were planned. Cycles were repeated every 3 weeks for a total of 4 cycles. Eligible subtypes were retroperitoneal liposarcoma, leiomyosarcoma, and unresectable/metastatic high-grade chondrosarcoma. Results: Thirteen patients were enrolled: 7 chondrosarcoma, 4 liposarcoma, and 2 leiomyosarcoma. In 46 cycles administered, the most relevant grade 3/4 adverse effects per patient were neutropenia 54%, febrile neutropenia 15%, and asthenia 8%. No cardiac toxicity was observed. Only one doselimiting toxicity (febrile neutropenia) was reported in the third dose level. With regard to efficacy, 1 partial response (1 liposarcoma), 9 stable diseases (5 chondrosarcoma, 2 liposarcoma, 1 leiomyosarcoma), and 3 progressive diseases (2 chondrosarcoma and 1 leiomyosarcoma) were present. ABCB1 and ABCC1 RNA expression levels decreased by 58.47-fold and 1.47-fold, respectively, on day 5 of the cycle. Conclusions: Combination of MRP-1/P-gp inhibitor, nilotinib, as coadjuvant with doxorubicin is feasible; it appears not to add substantial toxicity compared with doxorubicin alone. Pharmacodynamic study supports this concept. The recommended dose for the phase II part for doxorubicin was 75 mg/m(2). (C) 2018 AACR. |
| تدمد: | 1078-0432 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=RECOLECTA___::f8632c7ed9bc754bd0146dd5f22f740a https://fundanet.fihgu.san.gva.es/publicaciones/ProdCientif/PublicacionFrw.aspx?id=1321 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.RECOLECTA.....f8632c7ed9bc754bd0146dd5f22f740a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10780432 |
|---|