Cetuximab in combination with irinotecan/5-fluorouracil/folinic acid (FOLFIRI) in the initial treatment of metastatic colorectal cancer: a multicentre two-part phase I/II study.

BACKGROUND: This study was designed to investigate the efficacy and safety of the epidermal growth factor receptor (EGFR) inhibitor cetuximab combined with irinotecan, folinic acid (FA) and two different doses of infusional 5-fluorouracil (5-FU) in the first-line treatment of EGFR-detectable metastatic colorectal cancer. METHODS: The 5-FU dose was selected on the basis of dose-limiting toxicities (DLTs) during part I of the study. Patients received cetuximab (400 mg/m2 initial dose and 250 mg/m2/week thereafter) and every 2 weeks irinotecan (180 mg/m2), FA (400 mg/m2) and 5-FU (either low dose [LD], 300 mg/m2 bolus plus 2,000 mg/m2 46-hour infusion, n = 7; or, high-dose [HD], 400 mg/m2 bolus plus 2,400 mg/m2; n = 45). RESULTS: Only two DLTs occurred in the HD group, and HD 5-FU was selected for use in part II. Apart from rash, commonly observed grade 3/4 adverse events such as leucopenia, diarrhoea, vomiting and asthenia occurred within the expected range for FOLFIRI. Among 52 patients, the overall response rate was 48%. Median progression-free survival (PFS) was 8.6 months (counting all reported progressions) and the median overall survival was 22.4 months. Treatment facilitated the resection of initially unresectable metastases in fourteen patients (27%): of these, 10 patients (71%) had no residual tumour after surgery, and these resections hindered the estimation of PFS. CONCLUSION: The combination of cetuximab and FOLFIRI was active and well tolerated in this setting. Initially unresectable metastases became resectable in one-quarter of patients, with a high number of complete resections, and these promising results formed the basis for the investigation of FOLFIRI with and without cetuximab in the phase III CRYSTAL trial.

Ovarian cancer in Europe: Cross-sectional trends in incidence and mortality in 28 countries, 1953-2000.

We have considered trends in incidence and mortality in 28 European countries using incidence data from successive volumes of Cancer Incidence in Five Continents and mortality from the WHO database. Countries with the highest rates in the early 1960s included the Nordic countries, Austria, Germany and the United Kingdom, but trends in these areas have tended to decline over recent calendar periods, particularly with regard to mortality. Southern European countries showed upward trends, at least until the early 1980s for France and Italy. Likewise, in most central and eastern European countries, ovarian cancer incidence and mortality rates were originally relatively low, but tended to rise over time. Falls in mortality, but not in incidence, over recent years were observed in the Czech Republic and Hungary. In several countries, mainly in northern Europe, trends were more favorable at younger age (25-49 years) than in the subsequent age groups. Thus, recent trends in ovarian cancer have led to a leveling of rates across various areas of the continent, although a 2.5-fold variation was still observed in the late 1990s between the highest mortality rate of 9.3/100,000 in Denmark and the lowest one of 3.6 in Portugal. These patterns should be viewed in the light of an observed reduction in parity, mainly in southern and eastern Europe, and the spread of oral contraceptive use, mainly in northern Europe, since these are the best recognized protective factors with regard to ovarian carcinogenesis. The declining mortality trends can also in part be ascribed to improvements in treatment.