The efficacy of CPT-11 (Campto, irinotecan) given as a single agent has been assessed in three phase II clinical studies of patients with advanced colorectal cancer conducted in Japan, Europe and the U.S. Among a total of 337 evaluable patients treated with CPT-11 in dosage schedules of 100-150 mg/m2 weekly or bi-weekly (Japan, n = 63; U.S., n = 118) or 350 mg/m2 every 3 weeks (Europe, n = 156), overall objective response rates ranged from 17 to 27% and the median duration of response was approximately 7-9 months. Prior treatment with chemotherapy did not preclude a response to CPT-11 as evidenced by response rates of 14 to 22% and response durations of approximately 6-8 months in this cohort. In the European study, comparison of chemotherapy-naive patients with those who had received only one 5-fluorouracil (5-FU)-based regimen revealed similar response rates (22 and 20%) and of note, CPT-11 maintained its activity in pretreated patients who had previously experienced progressive disease. Together, these results suggest a lack of cross-resistance between the two agents. Leucopenia and delayed diarrhoea were the major adverse events observed in these studies, with grade 3-4 events occurring in 15-36% and 13-47% of patients, respectively. CPT-11, therefore, has significant activity in advanced colorectal cancer with response rates that are reproducible, durable and comparable to those achieved with 5-FU plus folinic acid in the first-line treatment of metastatic disease. Further work is needed to define the optimum dosage schedule for CPT-11 and also to assess fully the utility of CPT-11 in combination with other chemotherapeutic agents. Nevertheless, the activity of CPT-11 in patients refractory to treatment with 5-FU may be considered a significant advance, making it the first effective second-line agent in this setting.