PURPOSE To determine whether irinotecan plus oxaliplatin (IROX) is superior to 
irinotecan alone in patients with metastatic colorectal cancer (CRC) previously 
treated with single-agent fluoropyrimidines. PATIENTS AND METHODS A phase III, 
randomized, open-label, multicenter study of patients with metastatic or 
recurrent CRC that had progressed or recurred during or after adjuvant or 
first-line fluoropyrimidines (fluorouracil/leucovorin or capecitabine, the 
latter only for metastatic CRC). Patients received IROX (irinotecan 200 mg/m(2) 
plus oxaliplatin 85 mg/m(2)) or irinotecan alone (350 mg/m(2)) every 3 weeks.
RESULTS: At the data cutoff (when 447 of 628 randomly assigned patients had 
died), median overall survival was 13.4 months (95% CI, 12.4 to 14.7 months) and 
11.1 month (95% CI, 10.0 to 12.7 months) in the IROX and irinotecan groups, 
respectively (hazard ratio = 0.78; 95% CI, 0.65 to 0.94; P = .0072). Overall 
response rate (22% v 7%, respectively; P < .0001), median time to progression 
(5.3 v 2.8 months, respectively; P < .0001), and improvement in tumor-related 
symptoms (32% v 19%, respectively; P = .0072) were also improved with IROX as 
compared with irinotecan. With the exception of granulocytopenia (25% v 13%), 
diarrhea (28% v 23%), and sensory disturbances (5% v 0%), grade 3 to 4 
toxicities were comparable between the IROX and irinotecan groups, respectively. 
CONCLUSION IROX is an effective treatment for metastatic CRC that has progressed 
after first-line fluoropyrimidine therapy. IROX improves efficacy compared with 
irinotecan alone, providing an additional option in the postadjuvant or 
second-line treatment setting for patients who experience treatment failure with 
single-agent fluoropyrimidine therapy.