Irinotecan as second-line chemotherapy after failure to 5FU for metastaticcolorectal cancer: phase III trials

Treatments of advanced colorectal cancer progressing after a 5FU based chem otherapy have not been extensively studied. However, 5FU in continuous infu sion, L-OHP alone or in combination with 5FU and CPT11 have proved their ef ficacy in terms of tumor growth control and symptomatic effect. Irinotecan only has been evaluated prospectively in phase III studies. This paper reports the results of the two randomized European studies which have demonstrated the efficacy of irinotecan used at the dose of 350 mg/m( 2) administered over 30 minutes every 3 weeks in patients progressing after a 5FU-based chemotherapy. The first study compared irinotecan versus best supportive care in a group of 279 patients. It demonstrated an overall surv ival benefit (9.2 versus 6.5 months, P < 0.0001) with a one-year survival o f 36.2% for patients treated by irinotecan versus 13.8%. There was also a q uality of life benefit, especially for asthenia and pain in favor of the ir inotecan arm. The second study compared irinotecan to a second-line infusio nal 5FU and randomized 260 patients. Irinotecan treated patients lived for significantly longer than those on 5FU: median time of survival was 10.8 mo nths versus 8.5 months (p = 0.035). Survival at 1 year was increased from 3 2% in the 5FU arm to 45% in the irinotecan arm. Pain-free survival and symp tom-free survival were better for patients treated by irinotecan and the gl obal quality of life score was in favor of irinotecan irinotecan when assig ning null value to missing data due to death in both arms. Both treatments were equally well tolerated. There two randomized studies have proved the e fficacy of irinotecan ns second line chemotherapy for colorectal cancers pr ogressing under 5FU. Combination of irinotecan to 5FU and/or L-OHP have now to be evaluated in this situation.