Sorafenib: in advanced renal cancer.
black triangle Sorafenib is an oral multikinase inhibitor that targets the mitogen-activated protein kinase signalling pathway and receptor tyrosine kinases involved in tumour proliferation and angiogenesis.black triangle In the large, phase III, randomised, double-blind, multicentre Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET) of patients with advanced clear-cell renal cell cancer in whom previous systemic therapy had failed, median progression-free survival was doubled in patients receiving sorafenib compared with those receiving placebo (5.9 vs 2.8mo).black triangle Significantly more patients receiving sorafenib than those receiving placebo in the phase III trial experienced complete or partial responses or stable disease.black triangle Age, risk-assessment score, prior treatment, metastasis in lung or liver, or time from diagnosis did not affect the improved progression-free survival in sorafenib recipients.black triangle In a randomised, phase II discontinuation trial of patients with advanced renal cancer, in which only those showing stable disease with sorafenib were randomised to further sorafenib or placebo, more patients receiving sorafenib were free of progressive disease 12 weeks after randomisation than were those receiving placebo, and median progression-free survival was longer in sorafenib recipients.black triangle In clinical trials, most drug-related adverse events were mild to moderate in severity. Grade 3/4 hand-foot skin reaction and hypertension occurred more often with sorafenib than with placebo.
McKeage
Kate
K
Wolters Kluwer Health, Adis, Auckland, New Zealand. demail@adis.co.nz
Wagstaff
Antona J
AJ
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects; D000077157:Sorafenib
D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib; D020794:Receptor Protein-Tyrosine Kinases