title: Safety, efficacy and prognostic analyses of sunitinib in the post-marketing surveillance study of Japanese patients with gastrointestinal stromal tumor.
abstract: OBJECTIVE
  This study was conducted to expand the sunitinib safety database in Japanese imatinib-resistant/-intolerant gastrointestinal stromal tumor patients. Retrospective analyses investigated common adverse events as potential prognostic markers.
  
  
  METHODS
  Four hundred and seventy patients who received sunitinib between June 2008 and November 2009 were analyzed for safety, progression-free survival and overall survival; 386 for objective response rate; 88% received sunitinib on Schedule 4/2 starting at 50 mg/day.
  
  
  RESULTS
  No unexpected safety issues occurred. Grade ≥ 3 adverse events occurred in 70%, most commonly thrombocytopenia (33%), neutropenia (22%) and leukopenia (15%). Objective response rate was 20% (95% confidence interval 16-24). Median progression-free survival was 22.4 weeks (95% confidence interval, 21.7-24.0). The overall survival rate at 24 weeks was 91% (95% confidence interval, 88-94). Higher relative dose intensity (≥70 vs. <70%) during the first 6 weeks and better Eastern Cooperative Oncology Group performance status (0 vs. ≥1) were associated with longer progression-free survival (24.0 vs. 20.1 weeks; P = 0.011; and 24.1 vs. 16.9 weeks; P < 0.001) and higher 24-week overall survival rate (94 vs. 83%; P < 0.001; and 96 vs. 83%; P < 0.001). Increased progression-free survival and overall survival rates were associated with specific adverse events. Cox proportional hazard modeling adjusted for relative dose intensity and performance status established hand-foot syndrome (hazard ratio = 0.636; 95% confidence interval, 0.456-0.888) and leukopenia (hazard ratio = 0.683; 95% confidence interval, 0.492-0.948) occurring within 12 weeks were significantly correlated with increased progression-free survival.
  
  
  CONCLUSIONS
  Sunitinib showed good efficacy and tolerable safety. Factors associated with greater efficacy were relative dose intensity, performance status and specific early adverse events.
authors.affiliation: Department of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center, Kita-ku, Sapporo.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Komatsu
authors.affiliation: Pfizer Japan, Shibuya-ku, Tokyo emiko.ohki@pfizer.com.
authors.forename: Emiko
authors.initials: E
authors.lastname: Ohki
authors.affiliation: Pfizer Japan, Shibuya-ku, Tokyo.
authors.forename: Naomi
authors.initials: N
authors.lastname: Ueno
authors.affiliation: Pfizer Japan, Shibuya-ku, Tokyo.
authors.forename: Ai
authors.initials: A
authors.lastname: Yoshida
authors.affiliation: Pfizer Japan, Shibuya-ku, Tokyo.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Toyoshima
authors.affiliation: Pfizer Japan, Shibuya-ku, Tokyo.
authors.forename: Eiji
authors.initials: E
authors.lastname: Ueda
authors.affiliation: Pfizer Japan, Shibuya-ku, Tokyo.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Houzawa
authors.affiliation: Pfizer Japan, Shibuya-ku, Tokyo.
authors.forename: Kanae
authors.initials: K
authors.lastname: Togo
authors.affiliation: National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
authors.forename: Toshirou
authors.initials: T
authors.lastname: Nishida
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D044466:Asian People / Q000706:statistics & numerical data*; D018572:Disease-Free Survival; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy*; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy*; D060831:Hand-Foot Syndrome / Q000453:epidemiology / Q000209:etiology; D006801:Humans; D015994:Incidence; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000453:epidemiology; D011379:Prognosis; D016016:Proportional Hazards Models; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D000077210:Sunitinib; D013921:Thrombocytopenia / Q000139:chemically induced / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib
keywords: Japan; gastrointestinal stromal tumors; post-marketing; prognostic marker; sunitinib