title: Prospective observational study of imatinib therapy in Japanese patients with advanced gastrointestinal stromal tumors: long-term follow-up and second malignancy.
abstract: OBJECTIVE
  Limited data are available concerning long-term results of imatinib therapy in patients with advanced gastrointestinal stromal tumors. We aimed to clarify the long-term outcomes of imatinib therapy in Japanese patients with advanced gastrointestinal stromal tumors.
  
  
  METHODS
  A prospective, observational study of imatinib therapy for unresectable and metastatic gastrointestinal stromal tumors was conducted in our institution. Imatinib was initiated at a dose of 400 mg daily and continued until disease progression. Safety, efficacy and long-term tolerability and survival were evaluated in an intent-to-treat population. The median follow-up period in this study was 68 months.
  
  
  RESULTS
  Seventy patients were enrolled between December 2001 and December 2009. Treatment-related Grade 3/4 adverse events occurred in 49 patients (70.0%). Although 14 patients required adverse effect management with hospitalization, only 5 patients (7.1%) withdrew from the treatment owing to imatinib intolerance. The tumor response and clinical benefit rates were 61.4 and 85.7%, respectively. Thirty-seven patients (52.9%) maintained the treatment at 400 mg daily imatinib, whereas 33 patients (47.1%) had their dose reduced to 300 mg daily or less. The overall survival rate at 5 years was 60.9% and the median survival time was 70 months. The median progression-free survival time of all the 70 enrolled patients was 30 months. Seven patients (10.0%) suffered from second malignancies, including three patients with genitourinary carcinomas.
  
  
  CONCLUSIONS
  Despite the need for dose reduction, the long-term results of imatinib therapy for advanced gastrointestinal stromal tumors were good in Japanese patients. Physicians should pay attention to the occurrence of second malignancies during imatinib therapy for gastrointestinal stromal tumor patients.
authors.affiliation: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata City 951-8510, Niigata, Japan. kandat@med.niigata-u.ac.jp
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kanda
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Seiichi
authors.initials: S
authors.lastname: Hirota
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Yajima
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Kosugi
authors.forename: Manabu
authors.initials: M
authors.lastname: Ohashi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Suzuki
authors.forename: Yasuoki
authors.initials: Y
authors.lastname: Mashima
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ajioka
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Hatakeyama
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001549:Benzamides; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D000068877:Imatinib Mesylate; D007564:Japan / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000139:chemically induced*; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use*; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate