title: Pooled safety analysis of BAY 43-9006 (sorafenib) monotherapy in patients with advanced solid tumours: Is rash associated with treatment outcome?
abstract: 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 400mg 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.
authors.affiliation: Department of Internal Medicine and Medical Oncology, West German Cancer Center, University Medical School of Essen, Essen, Germany. dirk.strumberg@marienhospital-herne.de
authors.forename: D
authors.initials: D
authors.lastname: Strumberg
authors.forename: A
authors.initials: A
authors.lastname: Awada
authors.forename: H
authors.initials: H
authors.lastname: Hirte
authors.forename: J W
authors.initials: JW
authors.lastname: Clark
authors.forename: S
authors.initials: S
authors.lastname: Seeber
authors.forename: P
authors.initials: P
authors.lastname: Piccart
authors.forename: E
authors.initials: E
authors.lastname: Hofstra
authors.forename: D
authors.initials: D
authors.lastname: Voliotis
authors.forename: O
authors.initials: O
authors.lastname: Christensen
authors.forename: A
authors.initials: A
authors.lastname: Brueckner
authors.forename: B
authors.initials: B
authors.lastname: Schwartz
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000009:adverse effects*; D017321:Clinical Trials, Phase I as Topic; D004305:Dose-Response Relationship, Drug; D003875:Drug Eruptions / Q000209:etiology*; D005076:Exanthema / Q000139:chemically induced*; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects*; D000077157:Sorafenib; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib