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The combination of irinotecan plus 5-fluorouracil and folinic acid has clinical and survival benefits over 5-fluorouracil and folinic acid alone in the setting of first line treatment of metastatic colorectal cancer. The aim of this cost-effectiveness analysis was to compare the economic implications, from a UK health commissioner perspective, of the two treatment arms (de Gramont regimen) in this setting. Resource utilisation data collected prospectively during the study were used as a basis for estimating cumulative drug dosage, chemotherapy admistration, and treatment of complications during first line therapy. Resource utilisation associated with further chemotherapy in patients who had progressed during the study was derived from a retrospective case note review. Drug acquisition costs were derived from the British National Formulary (September, 2001) and unit costs for clinical consultation and services were taken from the latest relevant cost database. Cumulative costs per patient associated with further chemotherapy were lower in the irinotecan plus 5-fluorouracil and folinic acid treatment arm. Based on incremental costs per life-year gained of £14 794, the combination of irinotecan plus 5-fluorouracil and folinic acid can be considered cost-effective by commonly accepted criteria compared with 5-fluorouracil and folinic acid alone. Thus, clinical and economic data demonstrate that irinotecan, either in combination with irinotecan plus 5-fluorouracil and folinic acid in the first line setting or as monotherapy in the second line setting, has a major role in the management of metastatic colorectal cancer.

We investigated 2-weekly intravenous irinotecan combined with oral capecitabine in patients with advanced gastroesophageal adenocarcinoma. In phase I, doses were escalated in chemotherapy naïve or pretreated patients to establish maximum tolerated doses (MTD). In phase II, patients were treated at MTD as first-line therapy with the primary end point of RECIST response. Dose levels in phase I were as follows: Level 1: irinotecan 150 mg m À2 on day 1; capecitabine 850 mg m À2 12-hourly on days 1 -9. Level 2: as level 1 but capecitabine 1000 mg m À2 . Level 3: as level 2 but irinotecan 180 mg m À2 . Level 4: as level 3 but capecitabine 1250 mg m À2 . In phase I, 21 patients were entered. Maximum tolerated dose was level 3. Dose-limiting toxicities were lethargy, diarrhoea, vomiting and mucositis. In phase II, 31 patients were entered at level 3. During the first six cycles, 13 of these patients underwent dose reduction and three patients stopped treatment for toxicity. A further six patients stopped for progressive disease. The commonest grade 3 -4 toxicities were lethargy (20%), diarrhoea (17%), nausea (10%) and anorexia (10%). There were no treatment-related deaths. The response rate was 32% (95% CI 16 -52%). Median overall survival was 10 months. This regimen is active in gastroesophageal adenocarcinoma. However, using the MTD defined in phase I, fewer than 50% patients tolerated six cycles without modification in phase II; therefore, modification of these doses is recommended for further study.