title: Bevacizumab safety in Japanese patients with colorectal cancer.
abstract: BACKGROUND
  Bevacizumab (Avastin(®)) was approved in Japan in April 2007 for patients with advanced or metastatic colorectal cancer. To address the limited clinical experience in Japanese patients, a post-approval surveillance study was undertaken in bevacizumab-treated patients in Japan.
  
  
  METHODS
  Bevacizumab (5 or 10 mg/kg every 2 weeks) was administered with chemotherapy; patients were observed for 26 weeks from initiation of treatment. The primary objective was to investigate the incidence of adverse drug reactions, particularly those of interest for bevacizumab. Univariate and multivariate analyses were performed to identify potential risk factors for adverse drug reactions.
  
  
  RESULTS
  In total, 2712 patients were registered and 2696 patients were included in the safety analysis. Hypertension (13.1%), hemorrhage (10.5%) and proteinuria (4.5%) were the most common adverse drug reaction. The incidences of serious adverse drug reactions were low: gastrointestinal perforation occurred in 0.9% of patients, hemorrhage in 1.3%, arterial thromboembolic events in 0.3%, venous thromboembolic events in 1.3% and wound-healing complications in 0.4%. The incidence of bevacizumab-specific adverse drug reactions was not influenced by the bevacizumab dose. Multivariate analyses identified risk factors for the following adverse drug reactions: hypertension (prior/concurrent hypertension); tumor-associated bleeding (performance status, prior/concomitant anticoagulant or nonsteroidal anti-inflammatory drug use); proteinuria (sex, performance status, prior/concurrent diabetes and proteinuria); gastrointestinal perforation (primary tumor in situ, concurrent nonsteroidal anti-inflammatory drug use); venous thromboembolic event (treatment stage, port insertion).
  
  
  CONCLUSIONS
  The safety profile of bevacizumab-containing regimens in this Japanese population was comparable with studies performed in Western countries. Bevacizumab is generally well tolerated in Japanese patients with advanced or metastatic colorectal cancer.
authors.affiliation: Bevacizumab Appropriate Use Committee Department of Medical Oncology and Hematology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo khatake@jfcr.or.jp.
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Hatake
authors.affiliation: Bevacizumab Appropriate Use Committee Department of Gastroenterology, Gastrointestinal Oncology Division, National Cancer Center Hospital East, Chiba.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Doi
authors.affiliation: Bevacizumab Appropriate Use Committee Department of Surgical Specialties, Graduate School, Tokyo Medical and Dental University, Tokyo.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uetake
authors.affiliation: Drug Safety Division, Chugai Pharmaceutical Company, Tokyo.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Drug Safety Division, Chugai Pharmaceutical Company, Tokyo.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Ishihara
authors.affiliation: Bevacizumab Appropriate Use Committee Department of Medical Oncology and Hematology, Faculty of Medicine, Oita University, Oita, Japan.
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Shirao
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage / Q000009:adverse effects*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006333:Heart Failure / Q000139:chemically induced; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D007564:Japan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D011358:Product Surveillance, Postmarketing; D011507:Proteinuria / Q000139:chemically induced; D012307:Risk Factors
chemical_list: D020533:Angiogenesis Inhibitors; D009944:Organoplatinum Compounds; D000068258:Bevacizumab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
keywords: Japanese; adverse drug reactions; bevacizumab; colorectal cancer; post-marketing surveillance