CPT-11 (irinotecan) addition to bimonthly, high-dose leucovorin and bolus and continuous-infusion 5-fluorouracil (FOLFIRI) for pretreated metastatic colorectal cancer

CPT-11 (irinotecan) has shown activity in patients with advanced colorectal cancer resistant to leucovorin (LV) and 5-fluorouracil (5-FU). In this stu dy, the simplified bimonthly LV-5-FU regimen was combined with CPT-11 (FOLF IRI) as third-line therapy for patients with advanced colorectal cancer. Co ntinuous infusion of 5-FU was administered with disposable pumps as outpati ent therapy. FOLFIRI consisted of CPT-11 180 mg/m(2) as a 90-min infusion d ay 1; LV 400 mg/m(2) as a 2-h infusion during CPT-11, immediately followed by 5-FU bolus 400 mg/m(2) and 46-h continuous infusion of 2.4-3 g/m(2) ever y 2 weeks. Among the 33 patients treated, 2 had partial responses for an ov erall response rate of 6%; 20 patients were stabilised (61%) and 11 had dis ease progression (33%). From the start of FOLFIRI, median progression-free survival was 18 weeks and median survival was 43 weeks. For the 242 cycles analysed, NCI-CTC toxicities grade 3-4 per patient were nausea 15%, diarrho ea 12% and neutropenia 15%. Overall, 10 patients (30%) experienced grade 3- 4 toxicity. 7 patients (21%) had grade 2 alopecia. FOLFIRI generated activi ty and acceptable toxicity, in heavily pretreated patients, with limited di arrhoea, mostly asymptomatic neutropenia and manageable nausea and relative ly uncommon alopecia. This regimen is suitable for studies in chemotherapy- naive patients. (C) 1999 Elsevier Science Ltd. All rights reserved.