PMID- 22790797
OWN - NLM
STAT- MEDLINE
DCOM- 20121019
LR  - 20211021
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 107
IP  - 4
DP  - 2012 Aug 7
TI  - Phase I dose-escalation study of aflibercept in combination with docetaxel and 
      cisplatin in patients with advanced solid tumours.
PG  - 598-603
LID - 10.1038/bjc.2012.304 [doi]
AB  - BACKGROUND: This phase I cohort study investigated aflibercept (vascular 
      endothelial growth factor (VEGF) trap) plus docetaxel and cisplatin in patients 
      with advanced solid tumours. METHODS: Patients received intravenous aflibercept 
      4, 5, or 6 mg kg(-1) with docetaxel and cisplatin (75 mg m(-2) each) on day 1 of 
      a 3-week cycle until progressive disease or unacceptable toxicity. Primary 
      objectives were determining cycle 1 dose-limiting toxicities (DLTs) and the 
      aflibercept recommended phase II trial dose (RP2D) for this combination. RESULTS: 
      During the dose-escalation phase (n=16), there were two DLTs of febrile 
      neutropenia (at 4 and 5 mg kg(-1)). Granulocyte colony-stimulating factor 
      prophylaxis was subsequently recommended. The RP2D of aflibercept was established 
      at 6 mg kg(-1) and administered to 14 additional patients. The most frequent 
      grade 3/4 adverse events (AEs) were neutropenia (43.3%), stomatitis (20.0%), 
      asthenia/fatigue (20.0%), and hypertension (16.7%). All-grade AEs associated with 
      VEGF blockade included epistaxis (83.3%), dysphonia (70.0%), proteinuria (53.3%), 
      and hypertension (50.0%). There were five partial responses (16.7%) and 18 cases 
      of stable disease (60.0%) (lasting >3 months in 10 patients). There were no 
      pharmacokinetic (PK) interactions between the three drugs. CONCLUSION: 
      Aflibercept 6 mg kg(-1) with docetaxel and cisplatin 75 mg m(-2) every 3 weeks is 
      the RP2D based on tolerability, antitumour activity, and PKs.
FAU - Freyer, G
AU  - Freyer G
AD  - Universite de Lyon, Service d'oncologie medicale, Centre d'Investigation des 
      Therapeutiques en Oncologie et Hematologie, Centre Hospitalier Lyon-Sud, Pierre 
      Benite 69495, France. Gilles.Freyer@chu-lyon.fr
FAU - Isambert, N
AU  - Isambert N
FAU - You, B
AU  - You B
FAU - Zanetta, S
AU  - Zanetta S
FAU - Falandry, C
AU  - Falandry C
FAU - Favier, L
AU  - Favier L
FAU - Trillet-Lenoir, V
AU  - Trillet-Lenoir V
FAU - Assadourian, S
AU  - Assadourian S
FAU - Soussan-Lazard, K
AU  - Soussan-Lazard K
FAU - Ziti-Ljajic, S
AU  - Ziti-Ljajic S
FAU - Fumoleau, P
AU  - Fumoleau P
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20120712
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Taxoids)
RN  - 15C2VL427D (aflibercept)
RN  - 15H5577CQD (Docetaxel)
RN  - EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor)
RN  - Q20Q21Q62J (Cisplatin)
SB  - IM
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Cisplatin/*administration & dosage
MH  - Docetaxel
MH  - Drug Administration Schedule
MH  - Fatigue/chemically induced
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Neoplasms/*drug therapy
MH  - Neutropenia/chemically induced
MH  - Receptors, Vascular Endothelial Growth Factor
MH  - Recombinant Fusion Proteins/*administration & dosage
MH  - Taxoids/*administration & dosage
PMC - PMC3419955
EDAT- 2012/07/14 06:00
MHDA- 2012/10/20 06:00
PMCR- 2013/08/07
CRDT- 2012/07/14 06:00
PHST- 2012/07/14 06:00 [entrez]
PHST- 2012/07/14 06:00 [pubmed]
PHST- 2012/10/20 06:00 [medline]
PHST- 2013/08/07 00:00 [pmc-release]
AID - bjc2012304 [pii]
AID - 10.1038/bjc.2012.304 [doi]
PST - ppublish
SO  - Br J Cancer. 2012 Aug 7;107(4):598-603. doi: 10.1038/bjc.2012.304. Epub 2012 Jul 
      12.