title: A phase I study of axitinib (AG-013736) in combination with bevacizumab plus chemotherapy or chemotherapy alone in patients with metastatic colorectal cancer and other solid tumors.
abstract: BACKGROUND
  Axitinib and bevacizumab are targeted therapies against the vascular endothelial growth factor pathway.
  
  
  METHODS
  Patients with previously treated solid tumors received axitinib (starting dose 5 mg twice daily) combined with FOLFOX plus bevacizumab (1, 2, or 5 mg/kg, cohorts 1-3, respectively), FOLFIRI (cohort 4), or FOLFOX (cohort 5). Safety and pharmacokinetics were assessed.
  
  
  RESULTS
  Thirty patients were enrolled (n = 16, 8, and 6 for cohorts 1-3, 4, and 5, respectively). Plasma concentrations and pharmacokinetic (PK) parameters were similar when drugs were administered alone and in various combinations. Most treatment-emergent adverse events (AEs) were mild to moderate and clinically manageable (most common: nausea, fatigue, diarrhea, anorexia, hypertension). Two of the four patients receiving axitinib with FOLFOX plus 5 mg/kg bevacizumab experienced dose-limiting toxicity (DLT) of inability to resume treatment for 14 days following treatment interruption (associated AE: hypertension); the maximum tolerated dose of bevacizumab in this combination was 2 mg/kg. No DLTs occurred with axitinib plus FOLFIRI or FOLFOX. Ten patients had RECIST-confirmed partial tumor responses (objective response rate: 33.3%).
  
  
  CONCLUSIONS
  Axitinib is well tolerated in combination with FOLFOX, FOLFIRI, or FOLFOX plus 2 mg/kg bevacizumab. PK interactions appear to be absent.
authors: Section of Gastrointestinal Oncology, Nevada Cancer Institute, Las Vegas, NV. Electronic address: sunil.sharma@hci.utah.edu.
authors: S
authors: S
authors: Sharma
authors: Department of Internal Medicine, Eastern Carolina Internal Medicine, Pollocksville, NC.
authors: V
authors: V
authors: Abhyankar
authors: Department of Internal Medicine, Eastern Carolina Internal Medicine, Pollocksville, NC.
authors: R E
authors: RE
authors: Burgess
authors: Drug Development and Gastrointestinal Cancer Research, Sarah Cannon Research Institute, Nashville, TN.
authors: J
authors: J
authors: Infante
authors: Indiana Oncology Hematology Consultants, St Francis Cancer Care Center, Indianapolis, IN.
authors: R C
authors: RC
authors: Trowbridge
authors: Oncology Development, Pfizer, San Diego, CA.
authors: J
authors: J
authors: Tarazi
authors: Oncology Development, Pfizer, San Diego, CA.
authors: S
authors: S
authors: Kim
authors: Oncology Development, Pfizer, San Diego, CA.
authors: M
authors: M
authors: Tortorici
authors: Oncology Development, Pfizer, San Diego, CA.
authors: Y
authors: Y
authors: Chen
authors: Bay Area Cancer Research Group, Department of Medical Oncology and Hematology, Concord, CA, USA.
authors: R L
authors: RL
authors: Robles
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000077784:Axitinib; D000068258:Bevacizumab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D007191:Indazoles / Q000008:administration & dosage* / Q000009:adverse effects; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007093:Imidazoles; D007191:Indazoles; D009944:Organoplatinum Compounds; D000068258:Bevacizumab; D000077784:Axitinib; D002955:Leucovorin; D005472:Fluorouracil