3 The technologies
Carmustine implants
3.1 Carmustine implants (Gliadel, Link Pharmaceuticals) are biodegradable copolymer discs impregnated with an alkylating agent called carmustine. They are about the size of a 5-pence coin, and are implanted into the resection cavity at the time of surgery. Each implant contains 7.7 mg of carmustine, which interacts with DNA, thereby preventing the proliferation of cells.
3.2 Carmustine implants have a UK marketing authorisation for the treatment of newly diagnosed high-grade malignant glioma as an adjunct to surgery and radiation, and for the treatment of recurrent GBM as an adjunct to surgery.
3.3 Adverse effects include brain oedema, convulsions, healing abnormalities and intracranial infections. For full details of side effects and contraindications, see the summary of product characteristics.
3.4 The cost of one carmustine implant is £650.38 (excluding VAT; 'British national formulary [BNF]' 52nd edition). Up to eight implants may be used simultaneously, depending on the shape and size of the resection cavity. Costs may vary in different settings because of negotiated procurement discounts.
Temozolomide
3.5 Temozolomide (Temodal, Schering-Plough Ltd) undergoes hydrolysis in the body to produce monomethyl triazenoimidazole carboxamide (MTIC). MTIC is thought to act by methylation of DNA in a way that prevents cell division.
3.6 Temozolomide has a UK marketing authorisation for the treatment of newly diagnosed GBM concomitantly with radiotherapy, and subsequently as monotherapy treatment. It also has a UK marketing authorisation for the treatment of malignant glioma showing recurrence or progression after standard therapy.
3.7 Adverse effects include anorexia, constipation, fatigue, headache, lymphopenia, nausea, neutropenia, thrombocytopenia and vomiting. For full details of side effects and contraindications, see the summary of product characteristics.
3.8 Temozolomide is available as 5 mg, 20 mg, 100 mg and 250 mg tablets. It is administered at 75 mg/m2 daily for 42 days concomitantly with radiotherapy (60 Gy administered in 30 fractions), and then as monotherapy at 150 mg/m2 daily for 5 days, followed by 23 days without treatment, for a maximum of six cycles. The dose may be increased to 200 mg/m2 daily in the second and subsequent cycles.
3.9 The cost of temozolomide is £17.30 for 5 x 5 mg tablets, £69.20 for 5 x 20 mg tablets, £346.00 for 5 x 100 mg tablets and £865.00 for 5 x 250 mg tablets (excluding VAT; BNF 52). Costs may vary in different settings because of negotiated procurement discounts.