Pixantrone monotherapy for treating multiply relapsed or refractory aggressive non-Hodgkin's B‑cell lymphoma

Pixantrone (Pixuvri, Cell Therapeutics) is an aza‑anthracenedione analogue and inhibitor of topoisomerase II. The recommended dosage is pixantrone 50 mg/m² on days 1, 8 and 15 of each 28-day cycle for up to 6 cycles. It is administered intravenously. Pixantrone has a conditional marketing authorisation 'as monotherapy for the treatment of adult patients with multiply relapsed or refractory aggressive non-Hodgkin B‑cell lymphomas (NHL). The benefit of pixantrone treatment has not been established in patients when used as fifth line or greater chemotherapy in patients who are refractory to last therapy'. The European public assessment report noted pixantrone had a reduced benefit in patients pretreated with rituximab. The marketing authorisation is linked to results being provided from the phase 3 PIX306 trial, which is investigating pixantrone plus rituximab compared with gemcitabine plus rituximab in patients with relapsed or refractory aggressive non-Hodgkin's B‑cell lymphomas who have previously received a rituximab-containing regimen. Results are expected in 2015.

The summary of product characteristics states that the most common toxicity with pixantrone is bone marrow suppression (particularly the neutrophil lineage) and that other toxicities such as nausea, vomiting and diarrhoea are generally infrequent, mild, reversible, manageable and as expected in patients treated with cytotoxic agents. Although the occurrence of cardiac toxicity indicated by congestive heart failure appears to be lower than that expected with related drugs like anthracyclines, the summary of product characteristics recommends monitoring left ventricular ejection fraction. For full details of adverse reactions and contraindications, see the summary of product characteristics.

Pixantrone is priced at £553.50 per 20‑ml vial containing 29 mg free base pixantrone, which is equivalent to 50 mg pixantrone dimaleate (excluding VAT; BNF edition 66). The estimated cost of a course of treatment is £19,926 (costs calculated over 4 cycles using an average of 3 vials per dose based on the median length of treatment in the PIX301 trial, described in section 3.2). Costs may vary in different settings because of negotiated procurement discounts. The manufacturer of pixantrone has agreed a patient access scheme with the Department of Health that makes pixantrone available with a discount. The size of the discount is commercial in confidence. The Department of Health considered that this patient access scheme does not constitute an excessive administrative burden on the NHS.