PMID- 22333707
OWN - NLM
STAT- MEDLINE
DCOM- 20120329
LR  - 20211021
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 106
IP  - 4
DP  - 2012 Feb 14
TI  - A phase I, dose-escalation study of TB-403, a monoclonal antibody directed 
      against PlGF, in patients with advanced solid tumours.
PG  - 678-84
LID - 10.1038/bjc.2011.609 [doi]
AB  - BACKGROUND: TB-403 (RO 5323441), a humanised monoclonal antibody, is a novel 
      antiangiogenesis agent directed against placental growth factor. The safety, 
      pharmacokinetics (PK), and antitumour activity of TB-403 were assessed in a phase 
      I, dose-escalation study in patients with advanced solid tumours. METHODS: 
      Patients in sequential dose groups received either weekly doses of 1.25, 5.0, or 
      10 mg kg(-1) or doses of 20 or 30 mg kg(-1) every third week. RESULTS: 
      Twenty-three patients were enrolled and received TB-403. The most common adverse 
      events (AEs) were fatigue, constipation, pyrexia, dyspnoea, and nausea. One 
      serious AE, a lung embolus in a patient with non-small cell lung cancer treated 
      with 10 mg kg(-1) weekly, was deemed possibly related to TB-403. No dose-limiting 
      toxicities were observed, and a maximum-tolerated dose was not reached. The PK 
      parameters were dose linear and the terminal half-life values ranged from 9 to 14 
      days. Six patients exhibited stable disease for at least 8 weeks. Two patients, 
      (oesophageal squamous cell carcinoma and pancreatic adenocarcinoma) both treated 
      with 5 mg kg(-1) weekly, remained stable for 12 months. CONCLUSION: TB-403 
      treatment in this patient population is well tolerated, with a safety profile 
      distinct from that of vascular endothelial growth factor-axis inhibitors.
FAU - Lassen, U
AU  - Lassen U
AD  - Department of Oncology 5073, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, 
      Denmark. ulrik.lassen@rh.regionh.dk
FAU - Nielsen, D L
AU  - Nielsen DL
FAU - Sorensen, M
AU  - Sorensen M
FAU - Winstedt, L
AU  - Winstedt L
FAU - Niskanen, T
AU  - Niskanen T
FAU - Stenberg, Y
AU  - Stenberg Y
FAU - Pakola, S
AU  - Pakola S
FAU - Stassen, J-M
AU  - Stassen JM
FAU - Glazer, S
AU  - Glazer S
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
DEP - 20120124
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (PGF protein, human)
RN  - 0 (Pregnancy Proteins)
RN  - 144589-93-5 (Placenta Growth Factor)
RN  - 46MVG4H2LF (TB-403)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Angiogenesis Inhibitors/administration & dosage/adverse effects/*therapeutic use
MH  - Antibodies, Monoclonal/administration & dosage/adverse 
      effects/pharmacokinetics/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized/administration & dosage
MH  - Drug Administration Schedule
MH  - Female
MH  - Humans
MH  - Infusions, Intravenous
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Neoplasms/*drug therapy
MH  - Placenta Growth Factor
MH  - Pregnancy Proteins/*immunology
PMC - PMC3322959
EDAT- 2012/02/16 06:00
MHDA- 2012/03/30 06:00
PMCR- 2013/02/14
CRDT- 2012/02/16 06:00
PHST- 2012/02/16 06:00 [entrez]
PHST- 2012/02/16 06:00 [pubmed]
PHST- 2012/03/30 06:00 [medline]
PHST- 2013/02/14 00:00 [pmc-release]
AID - bjc2011609 [pii]
AID - 10.1038/bjc.2011.609 [doi]
PST - ppublish
SO  - Br J Cancer. 2012 Feb 14;106(4):678-84. doi: 10.1038/bjc.2011.609. Epub 2012 Jan 
      24.