Irinotecan: New results in the combination chemotherapy of colorectal cancer

Irinotecan is one of the newer cytostatic agents which have a clinically re levant antineoplastic activity in colorectal cancer. As single-agent irinot ecan induced an overall objective response rate of about 25% in chemonaive patients and of about 13% in 5-fluorouracil (5-FU)-pretreated patients. In the past years an increasing number of various combinations of irinoteca n with oxaliplatin, tomudex and especially 5-FU/folinic acid (FA) were inve stigated in phase I/II/III trials. These trials showed that these combinati ons are active and that the toxicity profile is acceptable and manageable. In phase II trials combinations of irinotecan plus 5-FU/FA induced overall objective response rates of 40-70% in chemonaive patients and of 20-30% in patients with prior 5-FU-based chemotherapies. Two large randomized trials compared the combination of irinotecan plus either bolus 5-FU/FA or 'infusi onal' 5-FU/FA with 5-FU/FA alone as first-line chemotherapy for metastatic disease. These two trials consistently showed that the combination was stat istically significantly superior to 5-FU/FA alone concerning the induction of objective responses (39 vs. 21% and 35 vs. 21%), median time to progress ion (7.0 vs. 4.3 months and 6.7 vs. 4.4 months), and median survival (14.8 vs. 12.6 months and 17.4 vs. 14.1 months). Quality of life analysis perform ed in both studies did not show that adding irinotecan to 5-FU/FA had a neg ative impact on overall quality of life parameters of the patients. Based o n these study results, the combination of irinotecan plus 5-FU/FA has to be considered as a new standard first-line treatment for patients with metast atic colorectal cancer.