3 The technologies

3 The technologies

Capecitabine

3.1 Capecitabine (Xeloda, Roche) is an orally administered precursor of the cytotoxic moiety 5-fluorouracil (5-FU). It is licensed for the adjuvant treatment of patients following surgery of stage III (Dukes' stage C) colon cancer, and for first-line monotherapy for metastatic colorectal cancer.

3.2 Capecitabine is contraindicated in patients with severe leucopenia, neutropenia or thrombocytopenia, and in patients with severe hepatic impairment or severe renal impairment. Dose-limiting toxicities include diarrhoea, abdominal pain, nausea, stomatitis and hand–foot syndrome (erythema and desquamation of the palms and the soles of the feet). Most adverse events are reversible and do not require permanent discontinuation of therapy, although doses may need to be withheld or reduced. For full details of side effects and contraindications, see the Summary of Product Characteristics.

3.3 The cost of 60 x 150-mg tablets and 120 x 500-mg tablets of capecitabine is £44.47 and £295.06, respectively (excluding VAT; British National Formulary [BNF] 50). For a person with a surface area of 1.75 m2 receiving the recommended dose, the cost of treatment with capecitabine is £301.46 per cycle. Costs may vary in different settings because of negotiated procurement discounts.

Oxaliplatin

3.4 Oxaliplatin (Eloxatin, Sanofi-Aventis) is a water-soluble platinum-based cytotoxic drug that prevents DNA replication, and hence cell division, by cross-linking DNA. Oxaliplatin in combination with intravenous 5-FU/FA is licensed for adjuvant treatment of stage III (Dukes' C) colon cancer after complete resection of primary tumour, and for the treatment of metastatic colorectal cancer. Neurotoxic side effects can be dose limiting. Acute paraesthesias or dysaesthesias of the extremities, triggered or exacerbated by cold temperatures, occur in 85–95% of people within hours of oxaliplatin infusion. These symptoms are normally mild and resolve within hours or days. However, with increasing cumulative dose, peripheral sensory symptoms increase in duration and intensity. Symptoms may progress to functional impairment. Cumulative neurotoxicity is reversible in most, but not all, cases, with regression of symptoms occurring in 4–6 months in about 80% of patients (see also 4.1.13). Other side effects include gastrointestinal disturbances and myelosuppression.

3.5 Oxaliplatin is contraindicated in patients who have myelosuppression before starting the first course, as evidenced by a baseline neutrophil count of less than 2 x 109 per litre and/or a platelet count of less than 100 x 109 per litre. It is also contraindicated in patients who have a peripheral neuropathy with functional impairment before the first course. For full details of side effects and contraindications, see the Summary of Product Characteristics.

3.6 The recommended dose for oxaliplatin is 85 mg/m2 when given in combination with 5-FU/FA. It is administered as an intravenous infusion over 2–6 hours every 2 weeks (usually for 6 months) followed by an infusion of 5-FU/FA.

3.7 Vials containing 50 mg and 100 mg cost £165 and £330, respectively (excluding VAT; BNF 50). For a person with a surface area of 1.75 m2 receiving the recommended dose, the cost of treatment with oxaliplatin is £495 per cycle. Costs may vary in different settings because of negotiated procurement discounts.