PMID- 18544172
OWN - NLM
STAT- MEDLINE
DCOM- 20080703
LR  - 20211020
IS  - 1471-2407 (Electronic)
IS  - 1471-2407 (Linking)
VI  - 8
DP  - 2008 Jun 10
TI  - A polymorphism of EGFR extracellular domain is associated with progression 
      free-survival in metastatic colorectal cancer patients receiving cetuximab-based 
      treatment.
PG  - 169
LID - 10.1186/1471-2407-8-169 [doi]
AB  - BACKGROUND: Cetuximab, a monoclonal antibody targeting Epidermal Growth Factor 
      Receptor (EGFR), is currently used in metastatic colorectal cancer (mCRC), but 
      predictive factors for therapeutic response are lacking. Mutational status of 
      KRAS and EGFR, and EGFR copy number are potential determinants of cetuximab 
      activity. METHODS: We analyzed tumor tissues from 32 EGFR-positive mCRC patients 
      receiving cetuximab/irinotecan combination and evaluable for treatment response. 
      EGFR copy number was quantified by fluorescence in situ hybridization (FISH). 
      KRAS exon 1 and EGFR exons coding for extracellular regions were sequenced. 
      RESULTS: Nine patients experienced an objective response (partial response) and 
      23 were considered as nonresponders (12 with stable disease and 11 with 
      progressive disease). There was no EGFR amplification found, but high polysomy 
      was noted in 2 patients, both of which were cetuximab responders. No EGFR 
      mutations were found but a variant of exon 13 (R521K) was observed in 12 
      patients, 11 of which achieved objective response or stable disease. 
      Progression-free and overall survivals were significantly better in patients with 
      this EGFR exon 13 variant. KRAS mutations were found in 14 cases. While there was 
      a trend for an increased KRAS mutation frequency in nonresponder patients (12 
      mutations out of 23, 52%) as compared to responder patients (2 out of 9, 22%), 
      authentic tumor response or long-term disease stabilization was found in KRAS 
      mutated patients. CONCLUSION: This preliminary study suggests that: an increase 
      in EGFR copy number may be associated with cetuximab response but is a rare event 
      in CRC, KRAS mutations are associated with low response rate but do not preclude 
      any cetuximab-based combination efficacy and EGFR exon 13 variant (R521K) may 
      predict for cetuximab benefit.
FAU - Goncalves, Anthony
AU  - Goncalves A
AD  - Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France. 
      goncalves.anthony2@orange.fr
FAU - Esteyries, Severine
AU  - Esteyries S
FAU - Taylor-Smedra, Brynn
AU  - Taylor-Smedra B
FAU - Lagarde, Arnaud
AU  - Lagarde A
FAU - Ayadi, Mounay
AU  - Ayadi M
FAU - Monges, Genevieve
AU  - Monges G
FAU - Bertucci, Francois
AU  - Bertucci F
FAU - Esterni, Benjamin
AU  - Esterni B
FAU - Delpero, Jean-Robert
AU  - Delpero JR
FAU - Turrini, Olivier
AU  - Turrini O
FAU - Lelong, Bernard
AU  - Lelong B
FAU - Viens, Patrice
AU  - Viens P
FAU - Borg, Jean-Paul
AU  - Borg JP
FAU - Birnbaum, Daniel
AU  - Birnbaum D
FAU - Olschwang, Sylviane
AU  - Olschwang S
FAU - Viret, Frederic
AU  - Viret F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080610
PL  - England
TA  - BMC Cancer
JT  - BMC cancer
JID - 100967800
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 7673326042 (Irinotecan)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - PQX0D8J21J (Cetuximab)
RN  - XT3Z54Z28A (Camptothecin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal/administration & dosage
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Camptothecin/administration & dosage/analogs & derivatives
MH  - Cetuximab
MH  - Colorectal Neoplasms/*drug therapy/enzymology/*genetics/pathology
MH  - Disease-Free Survival
MH  - ErbB Receptors/*genetics
MH  - Exons
MH  - Female
MH  - Gene Dosage
MH  - Genes, ras
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Irinotecan
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Neoplasm Metastasis
MH  - Polymorphism, Genetic
MH  - Protein Structure, Tertiary
MH  - Retrospective Studies
MH  - Treatment Outcome
PMC - PMC2432064
EDAT- 2008/06/12 09:00
MHDA- 2008/07/04 09:00
PMCR- 2008/06/10
CRDT- 2008/06/12 09:00
PHST- 2007/10/21 00:00 [received]
PHST- 2008/06/10 00:00 [accepted]
PHST- 2008/06/12 09:00 [pubmed]
PHST- 2008/07/04 09:00 [medline]
PHST- 2008/06/12 09:00 [entrez]
PHST- 2008/06/10 00:00 [pmc-release]
AID - 1471-2407-8-169 [pii]
AID - 10.1186/1471-2407-8-169 [doi]
PST - epublish
SO  - BMC Cancer. 2008 Jun 10;8:169. doi: 10.1186/1471-2407-8-169.