Fluorouracil leucovorin and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer

C Bokemeyer, I Bondarenko, A Makhson… - Journal of clinical …, 2009 - air.unimi.it
C Bokemeyer, I Bondarenko, A Makhson, JT Hartmann, J Aparicio, F De Braud, S Donea…
Journal of clinical oncology, 2009air.unimi.it
Purpose This randomized study assessed whether the best overall response rate (ORR) of
cetuximab combined with oxaliplatin, leucovorin, and fluorouracil (FOLFOX-4) was superior
to that of FOLFOX-4 alone as first-line treatment for metastatic colorectal cancer. The
influence of KRAS mutation status was investigated. Patients and Methods Patients received
cetuximab (400 mg/m (2) initial dose followed by 250 mg/m (2)/wk thereafter) plus FOLFOX-
4 (oxaliplatin 85 mg/m (2) on day 1, plus leucovorin 200 mg/m (2) and fluorouracil as a 400 …
Purpose This randomized study assessed whether the best overall response rate (ORR) of cetuximab combined with oxaliplatin, leucovorin, and fluorouracil (FOLFOX-4) was superior to that of FOLFOX-4 alone as first-line treatment for metastatic colorectal cancer. The influence of KRAS mutation status was investigated. Patients and Methods Patients received cetuximab (400 mg/m (2) initial dose followed by 250 mg/m (2)/wk thereafter) plus FOLFOX-4 (oxaliplatin 85 mg/m (2) on day 1, plus leucovorin 200 mg/m (2) and fluorouracil as a 400 mg/m (2) bolus followed by a 600 mg/m (2) infusion during 22 hours on days 1 and 2; n= 169) or FOLFOX-4 alone (n= 168). Treatment was continued until disease progression or unacceptable toxicity. KRAS mutation status was assessed in the subset of patients with assessable tumor samples (n= 233). Results The confirmed ORR for cetuximab plus FOLFOX-4 was higher than with FOLFOX-4 alone (46% v 36%). A statistically significant increase in the odds for a response with the addition of cetuximab to FOLFOX-4 could not be established (odds ratio= 1.52; P=. 064). In patients with KRAS wild-type tumors, the addition of cetuximab to FOLFOX-4 was associated with a clinically significant increased chance of response (ORR= 61% v 37%; odds ratio= 2.54; P=. 011) and a lower risk of disease progression (hazard ratio= 0.57; P=. 0163) compared with FOLFOX-4 alone. Cetuximab plus FOLFOX-4 was generally well tolerated. Conclusion KRAS mutational status was shown to be a highly predictive selection criterion in relation to the treatment decision regarding the addition of cetuximab to FOLFOX-4 for previously untreated patients with metastatic colorectal cancer.
Fluorouracil leucovorin and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer/C. Bokemeyer, I. Bondarenko, A. Makhson, JT Hartmann, J. Aparicio, F. De Braud, S. Donea, H. Ludwig, G. Schuch, C. Stroh, AH Loos, A. Zubel, P. Koralewski.-In: JOURNAL OF CLINICAL ONCOLOGY.-ISSN 0732-183X.-27: 5 (2009 Feb 10), pp. 663-671.
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