PMID- 19940012
OWN - NLM
STAT- MEDLINE
DCOM- 20100506
LR  - 20200712
IS  - 1569-8041 (Electronic)
IS  - 0923-7534 (Linking)
VI  - 21
IP  - 2
DP  - 2010 Feb
TI  - 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.
PG  - 297-304
LID - S0923-7534(19)38772-1 [pii]
LID - 10.1093/annonc/mdp489 [doi]
AB  - 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%). CONCLUSION: Axitinib is well 
      tolerated in combination with FOLFOX, FOLFIRI, or FOLFOX plus 2 mg/kg 
      bevacizumab. PK interactions appear to be absent.
FAU - Sharma, S
AU  - Sharma S
AD  - Section of Gastrointestinal Oncology, Nevada Cancer Institute, Las Vegas, NV. 
      Electronic address: sunil.sharma@hci.utah.edu.
FAU - Abhyankar, V
AU  - Abhyankar V
AD  - Department of Internal Medicine, Eastern Carolina Internal Medicine, 
      Pollocksville, NC.
FAU - Burgess, R E
AU  - Burgess RE
AD  - Department of Internal Medicine, Eastern Carolina Internal Medicine, 
      Pollocksville, NC.
FAU - Infante, J
AU  - Infante J
AD  - Drug Development and Gastrointestinal Cancer Research, Sarah Cannon Research 
      Institute, Nashville, TN.
FAU - Trowbridge, R C
AU  - Trowbridge RC
AD  - Indiana Oncology Hematology Consultants, St Francis Cancer Care Center, 
      Indianapolis, IN.
FAU - Tarazi, J
AU  - Tarazi J
AD  - Oncology Development, Pfizer, San Diego, CA.
FAU - Kim, S
AU  - Kim S
AD  - Oncology Development, Pfizer, San Diego, CA.
FAU - Tortorici, M
AU  - Tortorici M
AD  - Oncology Development, Pfizer, San Diego, CA.
FAU - Chen, Y
AU  - Chen Y
AD  - Oncology Development, Pfizer, San Diego, CA.
FAU - Robles, R L
AU  - Robles RL
AD  - Bay Area Cancer Research Group, Department of Medical Oncology and Hematology, 
      Concord, CA, USA.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20091125
PL  - England
TA  - Ann Oncol
JT  - Annals of oncology : official journal of the European Society for Medical 
      Oncology
JID - 9007735
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Imidazoles)
RN  - 0 (Indazoles)
RN  - 0 (Organoplatinum Compounds)
RN  - 2S9ZZM9Q9V (Bevacizumab)
RN  - C9LVQ0YUXG (Axitinib)
RN  - Q573I9DVLP (Leucovorin)
RN  - U3P01618RT (Fluorouracil)
RN  - Folfox protocol
SB  - IM
MH  - Adenocarcinoma/*drug therapy/pathology
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Angiogenesis Inhibitors/administration & dosage/adverse effects
MH  - Antibodies, Monoclonal/*administration & dosage/adverse effects
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse 
      effects
MH  - Axitinib
MH  - Bevacizumab
MH  - Colorectal Neoplasms/*drug therapy/pathology
MH  - Female
MH  - Fluorouracil/administration & dosage/adverse effects
MH  - Humans
MH  - Imidazoles/*administration & dosage/adverse effects
MH  - Indazoles/*administration & dosage/adverse effects
MH  - Leucovorin/administration & dosage/adverse effects
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Neoplasms/*drug therapy/pathology
MH  - Organoplatinum Compounds/administration & dosage/adverse effects
MH  - Treatment Outcome
EDAT- 2009/11/27 06:00
MHDA- 2010/05/07 06:00
CRDT- 2009/11/27 06:00
PHST- 2009/11/27 06:00 [entrez]
PHST- 2009/11/27 06:00 [pubmed]
PHST- 2010/05/07 06:00 [medline]
AID - S0923-7534(19)38772-1 [pii]
AID - 10.1093/annonc/mdp489 [doi]
PST - ppublish
SO  - Ann Oncol. 2010 Feb;21(2):297-304. doi: 10.1093/annonc/mdp489. Epub 2009 Nov 25.