scholarly journals Prognostic value of cetuximab-related skin toxicity in metastatic colorectal cancer patients and its correlation with parameters of the epidermal growth factor receptor signal transduction pathway: Results from a randomized trial of the GERMAN AIO CRC Stu

2012 ◽  
Vol 132 (1) ◽  
pp. 236-245 ◽  
Author(s):  
Sebastian Stintzing ◽  
Christine Kapaun ◽  
Rüdiger Paul Laubender ◽  
Andreas Jung ◽  
Jens Neumann ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Signal Transduction ◽  
Prognostic Value ◽  
Growth Factor Receptor ◽  
Signal Transduction Pathway ◽  
Skin Toxicity ◽  
Transduction Pathway ◽  
Receptor Signal ◽  
Epidermal Growth ◽  
Colorectal Cancer Patients

Treatment related changes of the serum epidermal growth factor receptor in advanced colorectal cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22096-e22096
Author(s):  
K. G. Spindler ◽  
D. Olsen ◽  
I. Brandslund ◽  
A. Jakobsen
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Prognostic Value ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Skin Toxicity ◽  
Epidermal Growth ◽  
Pre Treatment

e22096 Background: The epidermal growth factor receptor (EGFR) is an established target for therapy in colorectal cancer. The extracellular domain of the receptor is shed into circulation and detectable by ELISA. We investigated the changes in sEGFR levels during preoperative chemoradiation (CRT) in rectal cancer patients and third-line treatment with cetuximab and irinotecan (CETIRI) in advanced disease, to elucidate the predictive or prognostic value in these settings. Methods: We included 126 healthy controls and 118 patients with chemorefractory mCRC treated with cetuximab (initial 400/m2 mg followed by weekly 250mg/m2) and irinotecan (350 mg/m2 q3w). Response was evaluated according to RECIST. Furthermore, 114 patients with locally advanced rectal tumours were treated with CRT (60 Gy/30 fractions and concomitant uftoral (300 mg/m2)/leukovorin (22.5 mg) on treatment days, followed by surgery 8 weeks post-treatment and pathological tumour regression evaluation. Pre-treatment and consecutive samples were drawn at each visit. sEGFR was measured by ELISA. Median statistics and Kaplain-Mayer curves with log-rank testing for comparison of survival rates were performed. Results: There were significant differences between the median pre-treatment sEGFR levels in controls, rectal cancer and mCRC (58 ng/ml(56–59 95% C-I), 53 ng/ml(51–55 95% C-I) and 51 ng/ml(49–53 95% C-I), respectively, p<0.000). We detected a rapid increase in sEGFR by the first on- treatment values during CETIRI (p<0.001), and a correlation between the magnitude of increase and a higher degree of skin toxicity, a well known indicator of clinical benefit to EGFR inhibitors. sEGFR in rectal cancer patients displayed a decreasing tendency during CRT (p<0.001), but no correlation to local tumour response. Patients with baseline pre-treatment level > 43.4 ng/ml (mean sEGFR of control group-2xSD) had a significantly higher OS rate than patients with low baseline levels (93% and 59% respectively, HR 0.15, P=0.002). Conclusions: We report a rapid increase in sEGFR by the onset of CETIRI, which may indicate development of skin toxicity and thereby a better change of response. Furthermore, we suggest a potential prognostic value of sEGFR measurement during CRT in locally advanced rectal cancer. No significant financial relationships to disclose.

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