2 The technology
2.1 Trabectedin (Yondelis, Immedica) 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 £1,366.00 for a 1-mg (1,000-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 £3,458. The company has a commercial arrangement. This makes trabectedin available to the NHS with a discount. The size of the discount is commercial in confidence. It is the company's responsibility to let relevant NHS organisations know details of the discount.