Velcade Review

Multiple myeloma is the second most common haematologic malignancy, whose incidence increases with age with median age at diagnosis between 65 and 70 years. Cure for multiple myeloma is rare with few effective treatment options. Initial therapy for those young and fit, is myeloablation with high dose chemotherapy and subsequent rescue with autologous stem cell transplant (ASCT). For those unable to withstand this, combination chemotherapy is employed such as melphalan/prednisone and vincristine/doxorubicin/dexamethasone.

According to a recent review by Dicato M et al reported in Oncology published online in February 2007¹, Bortezomib (Velcade) which is a first-in-class proteosome inhibitor that specifically targets the ubiquitin-proteosome pathway, has shown remarkable efficacy in multiple myeloma. By targeting the proteosome and acting on multiple myeloma cells and the microenvironment, bortezomib has been shown to increase patients’ response especially those with relapse and refractory disease by inhibiting tumour growth, metastasis, and angiogenesis. They reviewed phase II and III trials and reported that patients who achieved complete response (CR) or partial response (PR) to bortezomib alone or in combination with other conventional chemotherapy, had significantly longer survival and acceptable toxicities. The review concluded that bortezomib, alone or in combination with dexamethasone, should be used as soon as possible in patients with multiple myeloma to increase response and prolong time to progression. Bortezomib has also shown significant efficacy as first-line treatment, and is effective and well tolerated in special patient population such as elderly and patients with renal impairment. Finally, the report suggested that “Bortezomib, with its targeted mechanism of action, excellent efficacy, and predictable, manageable toxicities may become the backbone of treatment for multiple myeloma”.According to another international multicentre phase II study, reported in the Journal of Oncology in October 2006², that evaluated response, overall survival and safety of bortezomib in patients with relapsed or refractory mantle cell lymphoma (MCL), confirmed the efficacy of bortezomib in relapsed/refractory MCL, with, manageable toxicity profile.Other studies are underway investigating combination of bortezomib with standard therapeutic agents in patients with untreated, relapsed and refractory MCL, with promising early results.References

1. Dicato M, Boccadoro M, al e. Management of Multiple Myeloma with Bortezomib: Experts Review the Data and Debate the Issue. Oncology [Review]. 2006;70:474-482.
2. Fisher RI, Bernstein SH, Kahl BS, Djulbegovic B, Robertson MJ, de Vos S, et al. Multicenter Phase II Study of Bortezomib in Patients With Relapsed or Refractory Mantle Cell Lymphoma. J Clin Oncol 2006; 24(30):4867-4874. Available from: http://jco.ascopubs.org/cgi/content/abstract/24/30/4867