3 The technologies
3.1 Bortezomib (Velcade, Janssen) is an anticancer drug that works by reversible proteasome inhibition. This inhibition leads to arrest of the cell cycle and apoptosis (cell death), which reduces tumour growth. Myeloma cells are more sensitive to the action of bortezomib than normal cells.
3.2 Bortezomib, in combination with melphalan and prednisone, is licensed for the treatment of patients with previously untreated multiple myeloma who are not eligible for high-dose chemotherapy with bone marrow transplant. Bortezomib is administered as an intravenous injection. Bortezomib is administered in combination with oral melphalan and oral prednisone for nine 6-week treatment cycles. In cycles 1–4, bortezomib is administered twice weekly (days 1, 4, 8, 11, 22, 25, 29 and 32). In cycles 5–9, bortezomib is administered once weekly (days 1, 8, 22 and 29). Melphalan and prednisone should both be given orally on days 1, 2, 3 and 4 of the first week of each cycle.
3.3 Bortezomib treatment is associated with peripheral neuropathy, thrombocytopenia, gastrointestinal effects (diarrhoea, nausea, vomiting and constipation) and other side effects. For full details of side effects and contraindications, see the summary of product characteristics (SPC).
3.4 The cost for a 3.5-mg vial of bortezomib is £762.38 (British national formulary [BNF] edition 61). Costs may vary in different settings because of negotiated procurement discounts.
3.5 Thalidomide (Thalidomide Celgene, Celgene) is an immunomodulatory agent. Its precise mechanism of action is under investigation and is currently unknown, but it is thought to have multiple actions, including anti-inflammatory activity and the ability to inhibit the growth and survival of myeloma cells and the growth of new blood vessels. It is also a non-barbiturate hypnotic sedative with central action.
3.6 Thalidomide in combination with melphalan and prednisone is licensed 'as first-line treatment of patients with untreated multiple myeloma, aged ≥ 65 years or ineligible for high dose chemotherapy'. The recommended dose is 200 mg daily, taken orally. A maximum number of 12 cycles of 6 weeks should be used. Thalidomide is prescribed and dispensed according to the Thalidomide Celgene Pregnancy Prevention Programme.
3.7 Thalidomide treatment is associated with thromboembolic events, peripheral neuropathy, rash/skin reactions, bradycardia, syncope and somnolence. Section 4.2 of the SPC outlines how to manage comorbidities such as risk of thromboembolic events, peripheral neuropathy or hepatic or renal impairment. For full details of side effects and contraindications, see the SPC.
3.8 The cost for a 28-capsule pack of 50-mg thalidomide capsules is £298.48 (BNF edition 61). Costs may vary in different settings because of negotiated procurement discounts.