2 The technology
2.1 Topotecan (Hycamtin, GlaxoSmithKline) prevents DNA replication in cancer cells by inhibiting the enzyme topoisomerase I. Topotecan in combination with cisplatin has a marketing authorisation for patients with carcinoma of the cervix recurrent after radiotherapy and for patients with stage IVB disease. The summary of product characteristics (SPC) states that patients with prior exposure to cisplatin require a sustained treatment-free interval to justify treatment with topotecan in combination with cisplatin.
2.2 The recommended dosage is 0.75 mg/m2/day topotecan, administered as a 30-minute intravenous infusion on days 1, 2 and 3 of each cycle. Cisplatin is administered after topotecan as an intravenous infusion on day 1 at a dosage of 50 mg/m2/day. Treatment should be repeated every 21 days for six cycles or until disease progresses. Topotecan should only be readministered if the neutrophil count is at least 1.5 x 109 per litre, the platelet count is at least 100 x 109 per litre, and the haemoglobin level is at least 9 g/100 ml (after transfusion if necessary). The SPC states that topotecan should only be used in units specialised in the administration of cytotoxic chemotherapy and it should only be administered under the supervision of a physician experienced in the use of chemotherapy.
2.3 Adverse effects commonly associated with topotecan include nausea, vomiting, neutropenia, leukopenia, anaemia, fatigue and alopecia. Topotecan is not recommended in patients with severe renal or hepatic impairment. Cisplatin causes nausea and vomiting in the majority of patients. Serious toxic effects of cisplatin on the kidneys, bone marrow and hearing function are common. Serum electrolyte disturbances, hyperuricaemia, allergic reactions and cardiovascular abnormalities have also been reported. For full details of adverse effects and contraindications, see the SPC.
2.4 The acquisition cost of topotecan is £97.65 for a 1-mg vial or £290.62 for a 4-mg vial (excluding VAT; 'British national formulary' [BNF] edition 57). The acquisition cost of cisplatin is £24.50 for a 50-mg vial or £50.22 for a 100-mg vial (excluding VAT; BNF edition 57). Assuming a body surface area of 1.7 m2, the total dose per cycle would be 3.825 mg topotecan (that is, 1.275 mg/day). Assuming excess topotecan is wasted after each dose, a total of six 1-mg vials would be required at a cost of £585.90. For cisplatin, the cost for the required 85 mg would be £49 for two 50-mg vials. The cost of topotecan for a full course of six cycles is £3515.40. Costs may vary in different settings because of negotiated procurement discounts.