Background: The aim of this study was to observe the effects of neoadjuvant therapy with irinotecan and 5-fluorouracil (5-FU)/folinic acid (FA) on the resection rate and survival of colorectal cancer patients with initially unresectable hepatic metastases. Patients and methods: Forty patients received neoadjuvant chemotherapy comprising irinotecan 180 mg/m² administered intravenously (i.v.) on day 1, FA 200 mg/m² i.v. on days 1 and 2, 5-FU 400 mg/m² i.v. bolus on days 1 and 2, and 5-FU 1200 mg/m² as a continuous 48-h i.v. infusion on day 1. The treatment was repeated every 2 weeks and response was assessed every 12 weeks (six cycles). Results: The objective response rate to chemotherapy was 47.5% (n = 19), with two complete responses and disease stabilization in 11 (27.5.%) patients. Responses were unconfirmed for 11 patients undergoing surgery within 2 weeks. Treatment was well tolerated and adverse events were typical of the chemotherapy agents used. Twenty-seven (67.5%) patients reported hematological toxicity (35.0% grade 3/4) and 14 (35.0%) reported gastrointestinal toxicity (12.5% grade 3/4). Thirteen patients (32.5%) underwent potentially curative liver resection following chemotherapy. Chemotherapy was particularly effective in patients with large metastases on entry to the study. The median time to progression is 14.3 months and, at a median follow-up of 19 months, all patients are alive. Conclusions: Neoadjuvant therapy with irinotecan combined with 5-FU/FA enabled a significant proportion of patients with initially unresectable liver metastases to undergo surgical resection. The effects of treatment on survival have yet to be determined.

Background: To identify the most effective of two combinations, irinotecan/5-fluorouracil (5-FU)/folinic acid (FA) and irinotecan/cisplatin, in the treatment of advanced gastric cancer, for investigation in a phase III trial. Patients and methods: Patients were randomized to receive irinotecan [80 mg/m² intravenously (i.v.)], FA (500 mg/m² i.v.) and a 22-h infusion of 5-FU (2000 mg/m² i.v.), weekly for 6 weeks with a 1-week rest, or irinotecan (200 mg/m² i.v.) and cisplatin (60 mg/m² i.v.), on day 1 for 3 weeks. Results: A total of 115 patients were eligible for analysis in the per-protocol population. The overall response rate in the irinotecan/5-FU/FA arm (n=59) was 42.4%, with a complete response rate of 5.1%. Corresponding figures for the irinotecan/cisplatin arm (n=56) were 32.1% and 1.8%, respectively. The median time to progression was 6.5 months (irinotecan/5-FU/FA) and 4.2 months (irinotecan/cisplatin) (P < 0.0001), with median survival times of 10.7 and 6.9 months, respectively (P=0.0018). The major toxicity was grade 3/4 neutropenia, which was more pronounced with irinotecan/cisplatin than with irinotecan/5-FU/FA (65.7% versus 27%). Diarrhea was the main grade 3/4 non-hematological toxicity with both irinotecan/5-FU/FA (27.0%) and irinotecan/cisplatin (18.1%). Conclusions: Both combinations were active, with acceptable safety profiles. Irinotecan/5-FU/FA was selected as the most effective combination for investigation in a phase III trial in advanced gastric cancer.

We have previously reported that neoadjuvant therapy with modified FOLFIRI enabled nearly a third of patients with metastatic colorectal cancer (mCRC) to undergo surgical resection of liver metastases. Here, we present data from the long-term follow-up of these patients. Forty patients received modified FOLFIRI: irinotecan 180 mg m⁻², day 1; folinic acid, 200 mg m⁻²; and 5-fluorouracil: as a 400 mg m⁻² bolus, days 1 and 2, and a 48-h continuous infusion 1200 mg m⁻², from day 1. Treatment was repeated every 2 weeks, with response assessed every six cycles. Resected patients received six further cycles of chemotherapy postoperatively. Nineteen (47.5%) of 40 patients achieved an objective response; 13 (33%) underwent resection. After a median follow-up of 56 months, median survival for all patients was 31.5 months: for non-resected patients, median survival was 24 months and was not reached for resected patients. Median time to progression was 14.3 and 5.2 months for all and non-resected patients, respectively. Median disease-free (DF) survival in resected patients was 52.5 months. At 2 years, all patients were alive (8 DF), and at last follow-up, eight were alive (6 DF). Surgical resection of liver metastases after neoadjuvant treatment with modified FOLFIRI in CRC patients achieved favourable survival times.