Panitumumab as a radiosensitizing agent in KRAS wild-type locally advanced rectal cancer.

Details

Serval ID
serval:BIB_473B6613DB5A
Type
Article: article from journal or magazin.
Collection
Publications
Title
Panitumumab as a radiosensitizing agent in KRAS wild-type locally advanced rectal cancer.
Journal
Targeted Oncology
Author(s)
Mardjuadi F.I., Carrasco J., Coche J.C., Sempoux C., Jouret-Mourin A., Scalliet P., Goeminne J.C., Daisne J.F., Delaunoit T., Vuylsteke P., Humblet Y., Meert N., van den Eynde M., Moxhon A., Haustermans K., Canon J.L., Machiels J.P.
ISSN
1776-260X (Electronic)
ISSN-L
1776-2596
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
10
Number
3
Pages
375-383
Language
english
Notes
Publication types: Journal ArticlePublication Status: ppublish
Abstract
Our goal was to optimize the radiosensitizing potential of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies, when given concomitantly with preoperative radiotherapy in KRAS wild-type locally advanced rectal cancer (LARC). Based on pre-clinical studies conducted by our group, we designed a phase II trial in which panitumumab (6 mg/kg/q2 weeks) was combined with preoperative radiotherapy (45 Gy in 25 fractions) to treat cT3-4/N + KRAS wild-type LARC. The primary endpoint was complete pathologic response (pCR) (H0 = 5 %, H1 = 17 %, α = 0.05, β = 0.2). From 19 enrolled patients, 17 (89 %) were evaluable for pathology assessment. Although no pCR was observed, seven patients (41 %) had grade 3 Dworak pathological tumor regression. The regimen was safe and was associated with 95 % of sphincter-preservation rate. No NRAS, BRAF, or PI3KCA mutation was found in this study, but one patient (5 %) showed loss of PTEN expression. The quantification of plasma EGFR ligands during treatment showed significant upregulation of plasma TGF-α and EGF following panitumumab administration (p < 0.05). At surgery, patients with important pathological regression (grade 3 Dworak) had higher plasma TGF-α (p = 0.03) but lower plasma EGF (p = 0.003) compared to those with grade 0-2 Dworak. Our study suggests that concomitant panitumumab and preoperative radiotherapy in KRAS wild-type LARC is feasible and results in some tumor regression. However, pCR rate remained modest. Given that the primary endpoint of our study was not reached, we remain unable to recommend the use of panitumumab as a radiosensitizer in KRAS wild-type LARC outside a research setting.
Pubmed
Web of science
Create date
16/01/2015 13:04
Last modification date
03/03/2018 16:49
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