[Relationship between Polymorphisms and the Efficacy of Cetuximab].
OBJECTIVE
Cetuximab has shown efficacy in patients with metastatic colorectal cancer (mCRC). Recent studies have demonstrated that cetuximab induces antibody-dependent cell-mediated cytotoxicity (ADCC), mediated via the fragment c gamma receptors(FcgR)in mCRC. Since the establishment of KRAS mutations as a major negative predictor of efficacy, additional biomarkers have been found to be useful for the improvement of selection of patients likely to be responsive to cetuximab. We investigated the relationship between polymorphisms and the outcome of mCRC patients treated with cetuximab.


METHODS
In this study, 57 patients were evaluated. The relationships of FcgR polymorphisms with response rate (RR), progression-free survival (PFS), and overall survival (OS) were analyzed.


RESULTS
The FcgR polymorphisms were not significantly related to RR, PFS, and OS. Compared with the other haplotypes, the haplotype containing the 131H and 158V alleles was related to a lower RR (p=0.018). The diplotypes containing 131H and 158V alleles had significantly lower RR than the other diplotypes (p=0.038).


CONCLUSIONS
Our data suggest that FcgR polymorphisms may be associated with the outcome of mCRC patients treated with cetuximab and FOLFIRI. However, these results are currently controversial, and detailed investigations are needed to confirm the relationship between FcgRs polymorphisms and cetuximab efficacy.
Dept. of Digestive Surgery and Surgical Oncology（SurgeryⅡ), Yamaguchi University Graduate School of Medicine.
Yuka
Y
Inoue
Shoichi
S
Hazama
Ryoichi
R
Tsunedomi
Shigeru
S
Takeda
Tomio
T
Ueno
Shigeru
S
Yamamoto
Shigefumi
S
Yoshino
Junichi
J
Sakamoto
Hideyuki
H
Mishima
Masaaki
M
Oka
Hiroaki
H
Nagano
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000068818:Cetuximab / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D011961:Receptors, Fc / Q000235:genetics*; D018631:ras Proteins / Q000235:genetics
C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D011961:Receptors, Fc; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab