Zoledronic acid improves survival in multiple myeloma patients versus the UK and European standard treatment of clodronic acid (sodium clodronate) in patients with multiple myeloma. Since overall survival in patients given zoledronic acid improved independently of prevention of skeletal-related events, the study shows that zoledronic acid has treatment benefits beyond bone health. These findings from the MRC Myeloma IX study are published Online First and in an upcoming Lancet, and presented at the American Society of Hematology meeting in Orlando, Florida. The Article is by Professor Gareth J Morgan, The Institute of Cancer Research, London, UK, and Professors Walter M Gregory and J Anthony Child, Clinical Trials Research Unit, University of Leeds, UK, and colleagues.

Bisphosphonates are a standard aspect of care for prevention of skeletal-related events in patients with advanced cancer. In multiple myeloma, malignant plasma cells in the bone marrow induce destruction of bone putting patients at high risk of fractures with severe consequences. Previous work has suggested that some bisphosphonates, including zoledronic acid and clodronic acid-may also cause destruction of cancer cells in addition to protecting bone health. Zoledronic acid ,in particular,has shown potential anticancer effects in preclinical and clinical studies. Bisphosphonates break the cycle of bone destruction and cancer growth that can result in skeletal-related events. Yet despite strong consensus that antimyeloma therapies should be given to symptomatic patients with multiple myeloma, no optimal regimen has emerged. In this study, the largest and most comprehensive yet undertaken in myeloma, the authors compared zoledronic acid and clodronic acid in multiple myeloma patients.

In this randomised controlled trial, 1960 patients were assessed: 981 receiving zoledronic acid, with 555 on intensive chemotherapy and 426 on non-intensive chemotherapy; and 979 receiving clodronic acid, with 556 on intensive chemotherapy and 423 on non-intensive chemotherapy. Patients spent a median time of 350 days on bisphosphonate treatment before disease progression, with a median of 3.7 years’ follow-up.

The researchers found that zoledronic acid reduced mortality by 16% versus clodronic acid, and extended median overall survival by 5•5 months (50 months versus 44.5 months). Zoledronic acid also significantly improved progression-free survival by 12% versus clodronic acid, and increased median progression-free survival by 2•0 months (the 2.0 months result being of borderline statistical significance). Rates of complete, very good partial, or partial response did not differ significantly (statistically) between the zoledronic acid and clodronic acid groups for patients receiving intensive induction chemotherapy (78% vs 76%) or non-intensive induction chemotherapy (50% vs 46%).

Both bisphosphonates were generally well tolerated, with similar occurrence of acute renal failure and treatment-emergent serious adverse events, but zoledronic acid was associated with higher rates of confirmed osteonecrosis of the jaw (4%) than was clodronic acid (

Source: The Lancet