title: Phase I Study of Axitinib in Combination with Cisplatin and Capecitabine in Patients with Previously Untreated Advanced Gastric Cancer.
abstract: This phase I trial evaluated the question of whether the standard starting dose of axitinib could be administered in combination with therapeutic doses of cisplatin/capecitabine in patients with previously untreated advanced gastric cancer, and assessed overall safety, pharmacokinetics, and preliminary antitumor activity of this combination.
  
  
  
  Patients in dose level (DL) 1 received axitinib 5 mg twice a day (days 1 to 21) with cisplatin 80 mg/m(2) (day 1) and capecitabine 1,000 mg/m(2) twice a day (days 1 to 14) in 21-day cycles. Maximum tolerated dose (MTD) was the highest dose at which ≤ 30% of the first 12 patients experienced a dose-limiting toxicity (DLT) during cycle 1. Ten additional patients were enrolled and treated at the MTD in order to obtain additional safety and pharmacokinetic data.
  
  
  
  Three DLTs occurred during cycle 1 in three (25%) of the first 12 patients: ruptured abdominal aortic aneurysm, acute renal failure, and > 5 consecutive days of missed axitinib due to thrombocytopenia. DL1 was established as the MTD, since higher DL cohorts were not planned. Common grade 3/4 non-hematologic adverse events in 22 patients treated at DL1 included hypertension (36.4%) and decreased appetite and stomatitis (18.2% each). Cisplatin/capecitabine slightly increased axitinib exposure; axitinib decreased capecitabine and 5-fluorouracil exposure. Eight patients (36.4%) each had partial response or stable disease. Median response duration was 9.1 months; median progression-free survival was 3.8 months.
  
  
  
  In patients with advanced gastric cancer, standard doses of axitinib plus therapeutic doses of cisplatin and capecitabine could be administered in combination. Adverse events were manageable.
authors: Department of Internal Medicine, Seoul National University Hospital and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors: Do-Youn
authors: DY
authors: Oh
authors: Division of Gastroenterology, National Cancer Center Hospital East, Chiba, Japan.
authors: Toshihiko
authors: T
authors: Doi
authors: Department of Medical Oncology, Oita University Faculty of Medicine, Yufu, Japan.
authors: Kuniaki
authors: K
authors: Shirao
authors: Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
authors: Keun-Wook
authors: KW
authors: Lee
authors: Department of Internal Medicine, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
authors: Sook Ryun
authors: SR
authors: Park
authors: Pfizer Oncology, San Diego, CA, USA.
authors: Ying
authors: Y
authors: Chen
authors: Pfizer Oncology, San Diego, CA, USA.
authors: Liqiang
authors: L
authors: Yang
authors: Pfizer Oncology, Milan, Italy.
authors: Olga
authors: O
authors: Valota
authors: Department of Internal Medicine, Seoul National University Hospital and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors: Yung-Jue
authors: YJ
authors: Bang
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D000069287:Capecitabine / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D012449:Safety; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology*
chemical_list: D000069287:Capecitabine; D002945:Cisplatin
keywords: Axitinib; Capecitabine; Cisplatin; Clinical trial; Pharmacokinetics; Phase I; Stomach neoplasms