A randomised phase III study on capecitabine, oxaliplatin and bevacizumab with or without cetuximab in first-line advanced colorectal cancer, the CAIRO2 study of the Dutch Colorectal Cancer Group (DCCG). An interim analysis of toxicity.
BACKGROUND
Targeting the vascular endothelial growth factor or the epidermal growth factor receptor (EGFR) has shown efficacy in advanced colorectal cancer (ACC), but no data are available on the combination of these strategies with chemotherapy in the first-line treatment. The CAIRO2 study evaluates the effect of adding cetuximab, a chimeric mAb against EGFR, to capecitabine, oxaliplatin and bevacizumab in the first-line treatment of ACC.


METHODS
In all, 755 patients were randomly assigned between treatment with capecitabine, oxaliplatin and bevacizumab with or without cetuximab. The primary end point is progression-free survival. We here present the toxicity results in the first 400 patients that entered the study.


RESULTS
The incidence of overall grade 3-4 toxicity was significantly higher in arm B compared with arm A (81% versus 72%, P = 0.03). This difference is fully attributed to cetuximab-related skin toxicity. The addition of cetuximab did not result in an increase of gastrointestinal toxicity or treatment-related mortality.


CONCLUSIONS
The addition of cetuximab to capecitabine, oxaliplatin and bevacizumab in the first-line treatment of ACC appears to be safe and feasible. No excessive or unexpected toxicity in the cetuximab-containing treatment arm was observed.
Tol
J
J
Department of Medical Oncology, University Medical Centre St Radboud, Nijmegen, The Netherlands.
Koopman
M
M
Rodenburg
C J
CJ
Cats
A
A
Creemers
G J
GJ
Schrama
J G
JG
Erdkamp
F L G
FL
Vos
A H
AH
Mol
L
L
Antonini
N F
NF
Punt
C J A
CJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D000068258:Bevacizumab; D000069287:Capecitabine; D002277:Carcinoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D003875:Drug Eruptions / Q000209:etiology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D012720:Severity of Illness Index; D016019:Survival Analysis; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D000068818:Cetuximab; D005472:Fluorouracil