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, J.T. Hartmann, J. Aparicio, F. De Braud, S. Donea, H. Ludwig, G. Schuch, C. Stroh, A.H. Loos, A. Zubel, P. Koralewski. - In: JOURNAL OF CLINICAL ONCOLOGY. - ISSN 0732-183X. - 27:5(2009 Feb 10), pp. 663-671.
|Titolo:||Fluorouracil leucovorin and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer|
|Parole Chiave:||Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Colorectal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Mutation; Neoplasm Metastasis; Organoplatinum Compounds; Patient Compliance; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); ras Proteins|
|Settore Scientifico Disciplinare:||Settore MED/06 - Oncologia Medica|
|Data di pubblicazione:||10-feb-2009|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1200/JCO.2008.20.8397|
|Appare nelle tipologie:||01 - Articolo su periodico|