Treatment

The antitumour activity of different doses of combined TRAIL and taurolidine was analysed in the HT1080 xenografts. In the first series, varying doses of TRAIL (0.2, 1 or 2 µg/injection) were applied i.p. with a consistent dose of taurolidine (30 mg/injection in the first 4-day cycle and 15 mg/injection in the second 4-day cycle) within a time range of 12 days in 40 mice bearing n=80 xenografts. From day 1 after tumour inoculation, TRAIL was administered daily at 0.2, 1 or 2 µg/injection in combination with 30 mg/injection taurolidine for 4 days. Following a break of 2 days, treatment was continued with administration of TRAIL at 0.2, 1 or 2 µg/injection and taurolidine at 15 mg/injection for another 4 days. Accordingly, the first series consisted of one control group and three treatment groups (each n=20) with different cumulative dosages of TRAIL (1.6, 8 or 16 µg) but the same cumulative dosage of taurolidine (180 mg). Similarly, in the second series, varying doses of taurolidine (15, 20 or 25 mg/injection) were applied with a consistent dose of TRAIL (2 µg/injection) within a time range of 12 days in 9 mice bearing a total of 18 xenografts. With the exception of dosage, all procedures were performed the same way as in the first series. The second series consisted of three treatment groups (each n=6) with different cumulative dosage of taurolidine (120 mg, 160 mg or 200 mg) but the same cumulative dosage of TRAIL (16 µg). Tumour area and body weight were recorded daily, feed and water usage weekly. At 12 days after the beginning of treatment, all surviving animals were euthanised and tumour, liver, heart, lung, kidney and skin samples were removed and histologically examined.