The role of irinotecan and oxaliplatin in the treatment of advanced colorectal cancer

Colorectal carcinoma is one of the most common malignancies in the western world, and although fluorouracil (5-FU) has been used in its treatment for almost 40 years, new agents with significant activity have been introduced recently. Irinotecan (CPT-11, Camptosar), a topoisomerase I inhibitor, admi nistered at 300 to 350 mg/m(2) every 3 weeks is significantly more active t han continuous-infusion 5-FU in patients who have experienced disease progr ession after conventional therapy with 5-FU. In comparison to best supporti ve care, irinotecan improves survival and preserves quality of life despite treatment-related toxicity. Moreover, the combination of irinotecan and 5- FU has been explored in a number of different schedules. In previously untr eated patients, overall response rates are high. Irinotecan can also be com bined with mitomycin (mitomycin-C [Mutamycin]), oxaliplatin, or raltitrexed (Tomudex). Oxaliplatin is a new-generation platinum compound that has demo nstrated activity against colorectal carcinoma in preclinical trials. It ha s been evaluated as a single agent against advanced colorectal carcinoma in the salvage setting and also in combination with 5-FU as initial therapy f or metastatic disease (where it shows significant activity). The toxicity p rofile of oxaliplatin (chiefly characterized by neurotoxicity) differs from that of irinotecan (primarily producing diarrhea) and the potential, there fore, exists for combining these agents or for exploiting their possible sy nergy with 5-FU. The introduction of these two new active agents of differe nt pharmacologic classes promises to enable significant improvements in the treatment of patients with colorectal carcinoma.