Erbitux - Abstract 664: Cetuximab in combination with irinotecan/5-fluorouracil (5-FU)/folinic acid (FA) (FOLFIRI) in the first-line treatment of metastatic colorectal cancer (mCRC)
Citation: European Journal of Cancer Supplements Volume 3, No. 2, October 2005, Page 188
M. Peeters1, J.-L. Raoul2, J.-L. van Laethem3, P. Rougier4, C. Brezault5, F. Husseini6, L. Cals7, A. Zubel8, J.-C. Vedovato9
1Ghent University Hospital, Dept. Gastroenterology/Hepatology, Gent, Belgium
2Centre E Marquis, Rennes, France
3Hôpital Erasme, Brussels, Belgium
4Hôpital A. Paré, Boulogne, France
5Hôpital Cochin, Paris, France
6Hôpital Pasteur, Colmar, France
7Hôpital Font Pré, Toulon, France
8Merck KGaA, Darmstadt, Germany
9Merck Lipha Santé, Paris, France
Background:
FOLFIRI is a standard option in the first-line treatment of mCRC.
Cetuximab (Erbitux®) is an IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR), which is commonly expressed in mCRC. Cetuximab is active in mCRC patients failing on irinotecan-based therapy.
This phase I/II trial investigated the safety and efficacy of cetuximab+FOLFIRI in the first-line treatment of EGFR-expressing mCRC.
Materials and Methods:
Patients with immunohistochemistry-determined EGFR-expressing mCRC, who had not been treated for metastatic disease, received cetuximab (initial dose 400 mg/m2 followed by 250 mg/m2/week).
FOLFIRI was given every 2 weeks: irinotecan 180 mg/m2, FA 400 mg/m2 and 5-FU 300 mg/m2 bolus plus 2,000 mg/m2/46-h infusion (low-dose, LD) or 400 mg/m2 bolus plus 2,400 mg/m2/46-h infusion (high-dose, HD).
The use of LD 5-FU was part of the early dose-finding phase of the study.
Results:
This analysis was performed on the per-protocol HD population of 42 patients:
64.3%/35.7% male/female, mean age 60.0 years, median KPS 100, 79% colon primary tumour.
There were 19 confirmed objective responses (all partial responses [PR]) (45.2%) and 16 patients with stable disease (SD) (38.1%), giving a disease control rate (complete response+PR+SD) of 83.3%.
The median response duration was 306 days (10 months), and median survival was 699 days (23 months).
10 patients (23.8%) were able to undergo resection of metastases for curative intent, 9 of whom had liver metastases.
There were 8 R0 resections.
Treatment was well tolerated.
66.7% of the 42 patients experienced grade 3/4 adverse events, the most frequent of which were leucopenia (16.7%), diarrhoea (14.3%), vomiting and intestinal obstruction (11.9% each), skin rash and abdominal pain (9.5% each), and asthenia and dyspnoea (7.1% each).
Conclusions:
Cetuximab+FOLFIRI, incorporating high-dose 5-FU, is a feasible and active combination for the first-line treatment of EGFR-expressing mCRC.
45.2% of patients achieved an objective response.
The median survival was 23 months and 23.8% patients were able to undergo resection of initially unresectable metastases. Based on these results, a new phase III trial was started.
ex2.excerptamedica.com*&selection=ABSTRACT&qryStartRowDetail=2 |
