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Targ Oncol (2015) 10:375383 DOI 10.1007/s11523-014-0342-9
ORIGINAL RESEARCH
Panitumumab as a radiosensitizing agent in KRAS wild-type locally advanced rectal cancer
Feby Ingriani Mardjuadi & Javier Carrasco & Jean-Charles Coche & Christine Sempoux &
Anne Jouret-Mourin & Pierre Scalliet & Jean-Charles Goeminne & Jean-Franois Daisne &
Thierry Delaunoit & Peter Vuylsteke & Yves Humblet & Nicolas Meert & Marc van den Eynde &
Anne Moxhon & Karin Haustermans & Jean-Luc Canon & Jean-Pascal Machiels
Received: 17 January 2014 /Accepted: 25 September 2014 /Published online: 11 October 2014 # Springer International Publishing Switzerland 2014
Abstract Our goal was to optimize the radiosensitizing potential of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies, when given concomitantly with pre-operative 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 %, =0.05, =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- and EGF following panitumumab administration (p<0.05). At surgery, patients with important pathological regression (grade 3 Dworak) had higher plasma TGF- (p=0.03) but lower plasma EGF
Electronic supplementary material The online version of this article (doi:http://dx.doi.org/10.1007/s11523-014-0342-9
Web End =10.1007/s11523-014-0342- 9) contains supplementary material, which is available to authorized users.
F. I. Mardjuadi : J.<P. MachielsInstitut de Recherche Exprimentale et Clinique, Ple dimagerie mdicale, radiothrapie et oncologie (IREC/MIRO), Universit catholique de Louvain, Brussels, Belgium
J. Carrasco : J.<L. CanonService doncologie mdicale, Grand Hpital de Charleroi (GhdC), Charleroi, Belgium
J.<C. CocheService de gastroentrologie, Clinique St-Pierre, Ottignies, Belgium
C. Sempoux : A. Jouret-MourinService danatomie pathologie, Cliniques universitaires St-Luc, Brussels, Belgium
C. Sempoux : A. Jouret-Mourin : P. Scalliet : Y. Humblet :
M. van den Eynde : A. MoxhonClinique...