EFFICACY OF CPT-11 (IRINOTECAN) AS A SINGLE-AGENT IN METASTATIC COLORECTAL-CANCER

The efficacy of CPT-11 (Campto(R), 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. Am ong a total of 337 evaluable patients treated with CPT-11 in dosage sc hedules of 100-150 mg/m(2) weekly or bi-weekly (Japan, n=63; U.S., n=1 18) or 350 mg/m(2) every 3 weeks (Europe, n=156), overall objective re sponse rates ranged from 17 to 27% and the median duration of response was approximately 7-9 months. Prior treatment with chemotherapy did n ot 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 coho rt. In the European study, comparison of chemotherapy-naive patients w ith those who had received only one 5-fluorouracil (5-FU)-based regime n revealed similar response rates (22 and 20%) and of note, CPT-11 mai ntained its activity in pretreated patients who had previously experie nced progressive disease. Together, these results suggest a lack of cr oss-resistance between the two agents. Leucopenia and delayed diarrhoe a were the major adverse events observed in these studies, with grade 3-4 events occurring in 15-36% and 13-47% of patients, respectively. C PT-11, therefore, has significant activity in advanced colorectal canc er with response rates that are reproducible, durable and comparable t o those achieved with 5-FU plus folinic acid in the first-line treatme nt of metastatic disease. Further work is needed to define the optimum dosage schedule for CPT-11 and also to assess fully the utility of CP T-11 in combination with other chemotherapeutic agents. Nevertheless, the activity of CPT-11 in patients refractory to treatment with 5-FU m ay be considered a significant advance, making it the first effective second-line agent in this setting. Copyright (C) 1996 Elsevier Science Ltd