Topotecan in advanced colorectal cancer

Colorectal cancer is the third most common cause of cancer-related death in both men and women. Surgery is the primary form of treatment, with greater than 90% of patients surviving 5 years or more. The remaining patients have metastatic disease, for which treatment options are limited. The fluoropyrimidine, 5-fluorouracil, elicits favorable tumor response rates in patients with metastatic disease, but has little impact on survival. Based on the observation that colorectal tumors have increased levels of topoisomerase I relative to normal tissue, investigations have focused on the camptothecin derivatives, particularly topotecan, as an effective treatment. Topotecan demonstrated antitumor activity in preclinical studies, causing significant growth delay of xenografts in thymectomized, irradiated mice. Clinical studies with topotecan have not yielded as promising results, with response rates of approximately 7% to 10%, but modifications in dosing schedule or combinations with other agents may enhance antitumor activity.