TOMUDEX (ZD1694) - RESULTS OF A RANDOMIZED TRIAL IN ADVANCED COLORECTAL-CANCER DEMONSTRATE EFFICACY AND REDUCED MUCOSITIS AND LEUKOPENIA

'Tomudex' (ZD1694), a direct and specific thymidylate synthase (TS) in hibitor entered phase III studies in November 1993. We present here th e first analysis of a randomised multicentre, international phase III study. 439 patients with previously untreated advanced colorectal canc er were randomised to Tomudex 3.0 mg/m(2) given once every 3 weeks or 5-fluorouracil (5-FU) 425 m/m(2) and leucovorin (LV) 20 mg/m(2) for 5 days (the Mayo regimen), given every 4-5 weeks. Patients were evaluate d weekly for toxicity and every 12 weeks for objective response. The t wo groups were well matched in terms of demographic characteristics. T he mean age of the patients was 61 years and most had either Liver (78 %) or lung (25-29%) metastases. Ninety seven per cent of patients allo cated to Tomudex and 94% of those allocated to 5-FU plus LV had measur able disease. Response was assessed using WHO/UICC criteria; all respo nse data were source validated; 19.8% of patients who received Tomudex and 12.7% of patients who received 5-FU plus LV had complete or parti al responses (P = 0.059, odds ratio 1.7, 95% confidence limits 0.98-2. 81). There were no statistically significant differences in time to pr ogression or survival between the two groups. Patients who received To mudex spent a substantially shorter time in hospital for dosing and ha d significantly lower rates of grade 3 and 4 toxicities such as leucop enia and mucositis. Patients who received Tomudex had a significantly higher incidence of reversible grade 3 or 4 increase in transaminases, which appear to be of limited clinical significance. Improvement in q uality of life, weight gain and performance status was seen in both gr oups. Tomudex has benefits in terms of higher response rates, reduced toxicity and more frequent palliative benefits when compared with 5-FU plus LV in the management of advanced colorectal cancer, and has a mo re convenient administration schedule.