2 The technology
2.1 Trabectedin (Yondelis, PharmaMar) is an alkylating agent, which affects cancer cells by damaging DNA. Trabectedin has a UK marketing authorisation for the treatment of patients with advanced soft tissue sarcoma after failure of anthracyclines and ifosfamide or who are unsuited to receive these agents. The marketing authorisation was granted under 'exceptional circumstances'. The summary of product characteristics (SPC) states that 'efficacy data are based mainly on liposarcoma and leiomyosarcoma patients'.
2.2 Trabectedin is contraindicated in people who have hypersensitivity to trabectedin or to any of the excipients, in those with concurrent serious or uncontrolled infection, in women who are breast-feeding, and in combination with yellow fever vaccine. The SPC states that trabectedin is not indicated for use in children and adolescents, and that creatine phosphokinase, hepatic function and haematological parameters should be monitored regularly during treatment. The SPC lists precautions for use of trabectedin in people with liver or kidney impairment. The SPC reports that the most common adverse reactions are nausea, fatigue, vomiting, weight loss (anorexia), neutropenia, thrombocytopenia, and increases in enzymes in blood indicating abnormal liver function. For full details of adverse events and contraindications, see the SPC.
2.3 The SPC for trabectedin states that 'the recommended dose is 1.5 mg/m2 body surface area, administered as an intravenous infusion over 24 hours with a 3-week interval between cycles.' The SPC also states that administration of trabectedin through a central venous line is 'strongly recommended'. Anti-emetic prophylaxis with intravenous dexamethasone (20 mg) must be administered to all patients 30 minutes before trabectedin treatment. Dexamethasone may also have hepatoprotective effects. The acquisition cost of trabectedin is £363.00 for a 250-microgram vial and £1366.00 for a 1-mg (1000-microgram) vial (excluding VAT; 'British national formulary' [BNF] edition 58). At a dose of 1.5 mg/m2, apatient with a body surface area of 1.7 m2 would need approximately 2.5 mg of trabectedin per cycle. One such infusion (using two 1-mg vials and two 250-microgram vials of trabectedin) would cost £3458. The manufacturer of trabectedin has agreed a patient access scheme with the Department of Health, in which the acquisition cost of trabectedin for treatment needed beyond the fifth cycle will be free to the NHS. The Department of Health considered that this patient access scheme does not constitute an excessive administrative burden on the NHS. The cost of treatment depends on the number of cycles used and costs may vary in different settings because of negotiated procurement discounts.