Nexavar for osteosarcoma – pro
Nexavar is currently FDA approved for renal cell carcinoma and hepatocellular carcinoma . Sorafenib (Nexavar) is designed to interfere with growth of new blood vessels and the growth of new cancer cells.Inhibition of KIT signaling provides a direct anti-tumor effect in most GIST tumors and inhibition of VEGF receptors and PDGFR-β provide antiangiogenesis effects (similar to Sutent). Since RAF is downstream of KIT, inhibition of RAF might also contribute an anti-tumor effect. While inhibition of PDGRF-β has been reported, inhibition of PDGFRα, an alternative target in about 5% of GISTs has NOT BEEN reported.
Because sacomas generally have a poor prognosis, Nexavar can sometimes be requested for use in sarcoma. For soteosarcoma, there is precliical activity reproted and a trial by Grignani suggeseted teh Nexavar can be active. Sorafenib demonstrated activity as a second- or third-line treatment in terms of PFS at 4 months with some unprecedented long-lasting responses
B . Kasper , T . Gil , V . D’Hondt , M . Gebhart , A . Awada Novel treatment strategies for soft tissue sarcoma Critical Reviews in Oncology/Hematology , Volume 62 , Issue 1 , Pages 9 – 15, 2007
Grignani G, Palmerini E, Dileo P, Asaftei SD, D’Ambrosio L, Pignochino Y, Mercuri M, Picci P, Fagioli F, Casali PG, Ferrari S, Aglietta M.
.A phase II trial of sorafenib in relapsed and unresectable high-grade osteosarcoma after failure of standard multimodal therapy: an Italian Sarcoma Group study.Ann Oncol. 2012 Feb;23(2):508-16
Ymera Pignochino et al, Sorafenib blocks tumour growth, angiogenesis and metastatic potential in preclinical models of osteosarcoma through a mechanism potentially involving the inhibition of ERK1/2, MCL-1 and ezrin pathways Molecular Cancer 2009, 8:118