The subcutaneous administration (under the skin) of bortezomib, a standard treatment in patients with multiple myeloma (cancer of the bone marrow), is as effective as standard intravenous delivery (into a vein) and could provide an easy home-based treatment option at a substantially reduced cost. These findings published in The Lancet Oncology also suggest that subcutaneous delivery has a better safety profile and reduces toxic effects - significantly lowering rates of peripheral neuropathy*, a common side-effect of bortezomib.

Bortezomib-based therapies are standard treatments in patients with newly diagnosed and relapsed multiple myeloma. As an alternative to the standard intravenous route, the subcutaneous delivery of bortezomib could improve patient convenience by eliminating the need for repeated intravenous access.

Philippe Moreau from University Hospital, Nantes, France and international colleagues designed a multicentre phase 3 trial to compare the efficacy and safety of subcutaneous and intravenous bortezomib at the recommended dose (1.3mg/m²) and schedule (twice each week) in patients with relapsed multiple myeloma. This study involved 222 patients from 53 centres across ten countries in Europe, Asia, and South America who were randomly assigned to receive eight cycles of subcutaneous (148) or intravenous (74) bortezomib. After four cycles of treatment, there was an overall response rate of 42% in both groups.

After a median follow-up of 11.8 months in the subcutaneous group and a year in the intravenous group, no significant differences in time to disease progression, progression-free survival, or overall survival were recorded.

Subcutaneous delivery had a better safety profile with lower rates of grade 3 or worse side-effects (57% vs 70%); there were also fewer dose reductions and discontinuations because of adverse events and subcutaneous injection was locally well tolerated.

Importantly, peripheral neuropathy, a significant side-effect of bortezomib, was significantly less common with subcutaneous delivery (38% vs 53%), despite similar rates of potential risk factors in each group.

The authors say: "Subcutaneous administration...in conjunction with dosing or schedule modifications could further reduce neuropathy side-effects to a level such that potential peripheral neuropathy risk factors no longer constitute a limiting factor for selection of bortezomib treatment."

They conclude: "The increased convenience of subcutaneous administration might also be relevant for investigation in settings such as maintenance therapy. This new route of administration could favour home administration of the drug, with substantial cost reduction and greatly improved patient convenience."

Commenting on the research, Dr María-Victoria Mateos from the University Hospital of Salamanca, Salamanca, Spain says: "The study...represents a further step towards the optimisation of bortezomib use, offering a more convenient route of administration, fewer side-effects, and similar or even improved efficacy. However, this route should not be implemented in routine practice until it has been approved. Above all, patient education and close monitoring programmes must continue, in conjunction with developing dose-modification guidelines that might avoid and reduce side-effects, to avoid converting a step forward into a step back."

*Peripheral neuropathy results from damage to the peripheral nerves and causes weakness, numbness, and pain in the hands and feet.

Article: http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70081-X/abstract