2 The technology
2.1 Bortezomib is a highly selective proteasome inhibitor specifically designed to inhibit the chymotrypsin‑like activity of the 26S proteasome in mammalian cells. This proteasome is a large protein complex that degrades unneeded or damaged proteins tagged with ubiquitin. The ubiquitin–proteasome pathway plays an essential role in many cellular processes, including the cell cycle. Bortezomib (Velcade, Janssen) has a marketing authorisation for treating adults with previously untreated mantle cell lymphoma for whom haematopoietic stem cell transplantation is unsuitable.
2.2 The summary of product characteristics includes the following adverse reactions for bortezomib: nausea, diarrhoea, constipation, vomiting, fatigue, fever, thrombocytopenia, anaemia, neutropenia, peripheral neuropathy (including sensory), headache, paraesthesia, decreased appetite, shortness of breath, rash, shingles and muscle pain. For full details of adverse reactions and contraindications, see the summary of product characteristics.
2.3 Bortezomib costs £762.38 for a 3.5‑mg vial (excluding VAT; British national formulary [BNF] edition 70). According to the summary of product characteristics, bortezomib should be given by intravenous or subcutaneous injection at the recommended dose of 1.3 mg/m2 body surface area twice weekly for 2 weeks on days 1, 4, 8, and 11, followed by a 10‑day rest period on days 12–21. This 3‑week period is considered a treatment cycle. Six cycles are recommended, although for people with a response first documented at cycle 6, 2 additional cycles may be given. There should be at least 72 hours between doses of bortezomib. Rituximab (at 375 mg/m2), cyclophosphamide (at 750 mg/m2) and doxorubicin (at 50 mg/m2) are administered on day 1 of each bortezomib 3‑week treatment cycle as intravenous infusions. Prednisone is administered orally at 100 mg/m2 for the first 5 days of each bortezomib cycle. Dose adjustment for bortezomib can be made in the event of toxicity. Full details of dose adjustments are given in the summary of product characteristics. Costs may vary in different settings because of negotiated procurement discounts.