3 The technology

3.1 Capecitabine

3.1.1 Capecitabine (Xeloda) is a fluoropyrimidine carbamate precursor of 5-FU. It is given orally and is converted via several enzymatic steps to give intratumoural release of 5-FU. The enzyme involved in the final conversion to 5-FU, thymidine phosphorylase, is found at higher levels in tumour tissues than in normal tissue, thereby reducing systemic exposure to 5-FU.

3.1.2 Capecitabine is indicated for first-line monotherapy of metastatic colorectal cancer. The recommended dose of capecitabine is 1250 mg/m2 twice daily for 14 days, followed by a 7-day rest period before another cycle of treatment.

3.1.3 The listed costs of 60 150-mg tablets and 120 500-mg tablets of capecitabine are £44 and £295 respectively (excluding VAT; British National Formulary 44, September 2002). Based on an assumed body surface area of 1.7 m2, the acquisition cost (excluding VAT) of treating an individual with capecitabine for 105 days (five cycles) is £1463. Costs may vary in different settings because of negotiated procurement discounts.

3.2 Tegafur with uracil

3.2.1 Tegafur is a 5-FU prodrug, meaning that after administration it is metabolised into the pharmacologically active compound 5-FU. Tegafur is given in combination with uracil, which inhibits the degradation of 5-FU, resulting in sustained higher levels of 5-FU in tumour cells. FA is usually added to the tegafur and uracil (UFT) combination to act as a modulator. These drugs can be taken orally.

3.2.2 UFT (Uftoral) is indicated for first-line treatment of metastatic colorectal cancer in combination with FA. Each capsule contains tegafur 100 mg plus uracil 224 mg.

3.2.3 The recommended dose of UFT is tegafur 300 mg/m2 (with uracil 672 mg/m2) daily, combined with oral FA 90 mg/day, given in three divided doses (preferably every 8 hours) for 28 days. Subsequent courses are repeated at 7-day intervals, giving a treatment cycle of 35 days.

3.2.4 The list cost of 21 UFT tablets is £67 (Monthly Index of Medical Specialties, February 2003). Based on an assumed body surface area of 1.7 m2, the acquisition cost (excluding VAT) of treating an individual with UFT for 105 days (three cycles) is £1358. FA obtained at a cost of £3.78 per 15-mg tablet incurs an additional cost of up to £1905. Costs may vary in different settings because of negotiated procurement discounts.