title: Efficacy and safety of axitinib in combination with gemcitabine in advanced pancreatic cancer: subgroup analyses by region, including Japan, from the global randomized Phase III trial.
abstract: OBJECTIVE
  Axitinib is a potent and selective inhibitor of vascular endothelial growth factor receptors 1-3. This analysis compared efficacy and safety of axitinib plus gemcitabine in patients with advanced pancreatic cancer from Japan, North America and the European Union, enrolled in a randomized Phase III study.
  
  
  METHODS
  Patients (n = 632), stratified by disease extent, were randomly assigned (1:1) to receive axitinib/gemcitabine or placebo/gemcitabine. Axitinib was administered at a starting dose of 5 mg orally twice daily and gemcitabine at 1000 mg/m(2) once weekly for 3 weeks in 4 week cycles. Primary endpoint was overall survival.
  
  
  RESULTS
  Among Japanese patients, median overall survival was not estimable (95% confidence interval, 7.4 months-not estimable) with axitinib/gemcitabine (n = 58) and 9.9 months (95% confidence interval, 7.4-10.5) with placebo/gemcitabine (n = 56) (hazard ratio 1.093 [95% confidence interval, 0.525-2.274]). Median survival follow-up (range) was 5.1 months (0.02-12.3) with axitinib/gemcitabine vs. 5.4 months (1.8-10.5) with placebo/gemcitabine. Similarly, no difference was detected in overall survival between axitinib/gemcitabine and placebo/gemcitabine in patients from North America or the European Union. Common adverse events with axitinib/gemcitabine in Japanese patients were fatigue, anorexia, dysphonia, nausea and decreased platelet count. Axitinib safety profile was generally similar in patients from the three regions, although there were differences in incidence of some adverse events. An exploratory analysis did not show any correlation between axitinib/gemcitabine-related hypertension and overall survival.
  
  
  CONCLUSIONS
  Axitinib/gemcitabine, while tolerated, did not provide survival benefit over gemcitabine alone in patients with advanced pancreatic cancer from Japan or other regions.
authors: Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka ioka-ta@mc.pref.osaka.jp.
authors: Tatsuya
authors: T
authors: Ioka
authors: Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo.
authors: Takuji
authors: T
authors: Okusaka
authors: Department of Gastroenterology, Kanagawa Cancer Center, Kanagawa.
authors: Shinichi
authors: S
authors: Ohkawa
authors: Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka.
authors: Narikazu
authors: N
authors: Boku
authors: Department of Clinical Oncology, Kawasaki Medical School, Okayama.
authors: Akira
authors: A
authors: Sawaki
authors: Pfizer Japan Inc., Tokyo, Japan.
authors: Yosuke
authors: Y
authors: Fujii
authors: Pfizer Japan Inc., Tokyo, Japan.
authors: Yoichi
authors: Y
authors: Kamei
authors: Pfizer Japan Inc., Tokyo, Japan.
authors: Satori
authors: S
authors: Takahashi
authors: Pfizer Japan Inc., Tokyo, Japan.
authors: Katsushi
authors: K
authors: Namazu
authors: Pfizer Japan Inc., Tokyo, Japan.
authors: Yoshiko
authors: Y
authors: Umeyama
authors: Pfizer Oncology, San Diego, CA, USA.
authors: Paul
authors: P
authors: Bycott
authors: Department of Medical Oncology, Kyorin University School of Medicine, Tokyo, Japan.
authors: Junji
authors: J
authors: Furuse
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000077784:Axitinib; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005062:European Union; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects; D007191:Indazoles / Q000008:administration & dosage / Q000009:adverse effects; D007564:Japan; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009656:North America; D016017:Odds Ratio; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality*; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D007093:Imidazoles; D007191:Indazoles; D003841:Deoxycytidine; D000077784:Axitinib; D000093542:Gemcitabine
keywords: Japanese; axitinib; gemcitabine; pancreatic cancer
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