cediranib + selumetinib

Combination of the oral VEGF receptor inhibitor cediranib and the oral MEK1/2 inhibitor selumetinib, investigated as an anti-angiogenic plus MAPK pathway–targeted regimen for advanced solid tumors and in chemoradiotherapy settings. Cediranib inhibits VEGFR-1/2/3 tyrosine kinases to block VEGF-driven angiogenesis; selumetinib inhibits MEK1/2 to suppress downstream ERK signaling in RAS/RAF/MEK/ERK pathway–activated cancers. A phase I study in advanced solid malignancies using continuous daily dosing found the combination not tolerable due to dose-limiting toxicities, with no maximum tolerated dose established; best responses were stable disease in some patients. Intermittent schedules were suggested for tolerability. A rectal cancer chemoradiotherapy trial arm planned cediranib or AZD6244 with capecitabine and radiotherapy but was terminated. These agents are developed by AstraZeneca, with selumetinib later marketed as Koselugo (selumetinib) for NF1 plexiform neurofibromas, though not in combination with cediranib.[2][3][1]

Brand names

Koselugo

Other names

cediranib maleate + selumetinib sulfate