title: A large-scale prospective registration study of the safety and efficacy of sorafenib tosylate in unresectable or metastatic renal cell carcinoma in Japan: results of over 3200 consecutive cases in post-marketing all-patient surveillance.
abstract: OBJECTIVE
  Real-life safety and efficacy of sorafenib in advanced renal cell carcinoma in a nationwide patient population were evaluated by post-marketing all-patient surveillance.
  
  
  METHODS
  All patients with unresectable or metastatic renal cell carcinoma in Japan who started sorafenib therapy from February 2008 to September 2009 were registered and followed for up to 12 months. Baseline characteristics, treatment status, tumor response, survival and safety data were recorded by the prescribing physicians.
  
  
  RESULTS
  Safety and efficacy were evaluated in 3255 and 3171 patients, respectively. The initial daily dose was 800 mg in 78.2% of patients. Median duration of treatment was 6.7 months and the mean relative dose intensity was 68.4%. Overall, 2227 patients (68.4%) discontinued the treatment by 12 months, half of which (52.0% of discontinued patients) were due to adverse events. The most common adverse drug reactions were hand-foot skin reaction (59%), hypertension (36%), rash (25%) and increase in lipase/amylase (23%). The median progression-free survival was 7.3 months (95% confidence intervals: 6.7-8.1), and the overall survival rate at 1 year was 75.4% (73.5-77.1). Prognostic factors for overall survival were mostly consistent with those in previous clinical trials in the univariate analysis and largely similar to those for progression-free survival and duration of treatment in the multivariate analysis.
  
  
  CONCLUSIONS
  Sorafenib for the treatment of advanced renal cell carcinoma under the labeled dose was feasible in daily medical practice, for its acceptable toxicity profile and favorable clinical benefit that were consistent with those in clinical trials.
authors.affiliation: Department of Strategic Investigation on Comprehensive Cancer Network, Interfaculty Initiative in Information Studies/Graduate School of Interdisciplinary Information Studies, The University of Tokyo, Tokyo akazah@med.rcast.u-tokyo.ac.jp.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Akaza
authors.affiliation: Department of Urology, Keio University School of Medicine, Tokyo.
authors.forename: Mototsugu
authors.initials: M
authors.lastname: Oya
authors.affiliation: Showa University School of Medicine, Tokyo.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Iijima
authors.affiliation: Department of Gastroenterology and Hepatology, Institute of Clinical Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki.
authors.forename: Ichinosuke
authors.initials: I
authors.lastname: Hyodo
authors.affiliation: Department of Pulmonary Medicine/Infection and Oncology, Internal Medicine, Nippon Medical School, Tokyo.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Gemma
authors.affiliation: Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Tokyo.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
authors.affiliation: Medical Affairs Oncology and Hematology, Bayer Yakuhin, Ltd., Osaka.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Adachi
authors.affiliation: Pharmacovigilance, Medical Affairs, Bayer Yakuhin, Ltd., Osaka.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Okayama
authors.affiliation: Clinical Statistics, Bayer Yakuhin, Ltd., Osaka, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sunaya
authors.affiliation: Pharmacovigilance, Medical Affairs, Bayer Yakuhin, Ltd., Osaka.
authors.forename: Lyo
authors.initials: L
authors.lastname: Inuyama
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary; D018572:Disease-Free Survival; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D007564:Japan; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000077157:Sorafenib; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib
keywords: molecularly targeted therapy; post-marketing surveillance; renal cell carcinoma; sorafenib tosylate