Pooled safety analysis of BAY 43-9006 (sorafenib) monotherapy in patients with advanced solid tumours: Is rash associated with treatment outcome?

In this analysis of the safety and efficacy of BAY 43-9006 (sorafenib) - a novel, oral multi-kinase inhibitor with effects on tumour and its vasculature - pooled data were obtained from four phase I dose-escalation trials. Time to progression (TTP) was compared in patients with/without ⩾grade 2 skin toxicity/diarrhoea. Grade 3 hand-foot skin reactions (HFS; 8%) and diarrhoea (6%) were common. At the recommended 400 mg bid dose for phase II/III trials (RDP), 15% of patients experienced grade 2/3 HFS, and 24% experienced grade 2/3 diarrhoea. Sorafenib induced stable disease for ⩾6 months in 12% of patients (6% stabilized for ⩾1 year). Patients receiving sorafenib doses at or close to the RDP, who experienced skin toxicity/diarrhoea, had a significantly increased TTP compared with patients without such toxicity (P < 0.05). Sorafenib was well tolerated at the RDP, and induced sustained disease stabilization, particularly in patients with skin toxicity/diarrhoea.