Lots of excitement and questions swirling around bisphosphonates lately. Aredia is the tried and true, less expensive, more conservative option. Zometa is much stronger than Aredia and requires a far shorter infusion time. Both drugs can cause osteonecrosis of the jaw (OMJ). A brand new alternative, Prolia should also be available soon. There are other new, developmental bisphosphonate and bisphosphonate alternatives on the horizon as well.
Good news–but confusing for doctors and patients alike! You will be hearing much more about this over the coming months. Here is a dosing study for the bisphosphonate, Aredia, from OncologySTAT. This study is a useful review for patients currently taking Aredia (pamidronate):
Effect of Pamidronate 30 mg Versus 90 mg on Physical Function in Patients With Newly Diagnosed Multiple Myeloma (Nordic Myeloma Study Group): A Double-Blind, Randomised Controlled Trial
Lancet Oncol. 2010 Oct 1;11(10):973-982, P Gimsing, K Carlson, I Turesson, P Fayers, A Waage, A Vangsted, A Mylin, C Gluud, G Juliusson, H Gregersen, H Hjorth-Hansen, I Nesthus, IM Dahl, J Westin, JL Nielsen, LM Knudsen, L Ahlberg, M Hjorth, N Abildgaard, NF Andersen, O Linder, F Wisløff
In this phase III double-blinded, randomized study low-dose pamidronate were as effective as the higher dose and was associated with lower incidence of osteonecrosis of the jaw.
Background: Compared with placebo, prophylactic treatment with bisphosphonates reduces risk of skeletal events in patients with multiple myeloma. However, because of toxicity associated with long-term bisphosphonate treatment, establishing the lowest effective dose is important. This study compared the effect of two doses of pamidronate on health-related quality of life and skeletal morbidity in patients with newly diagnosed multiple myeloma.
Methods: This double-blind, randomised, phase 3 trial was undertaken at 37 clinics in Denmark, Norway, and Sweden. Patients with multiple myeloma who were starting antimyeloma treatment were randomly assigned in a 1:1 ratio to receive one of two doses of pamidronate (30 mg or 90 mg) given by intravenous infusion once a month for at least 3 years. Randomisation was done by use of a central, computerised minimisation system. Primary outcome was physical function after 12 months estimated by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire (scale 0–100). All patients who returned questionnaires at 12 months and were still on study treatment were included in the analysis of the primary endpoint. This study is registered with ClinicalTrials.gov, number NCT00376883.
Findings: From January, 2001, until August, 2005, 504 patients were randomly assigned to pamidronate 30 mg or 90 mg (252 in each group). 157 patients in the 90 mg group and 156 in the 30 mg group were included in the primary analysis. Mean physical function at 12 months was 66 points (95% CI 62•9–70•0) in the 90 mg group and 68 points (64•6–71•4) in the 30 mg group (95% CI of difference −6•6 to 3•3; p=0•52). Median time to first skeletal-related event in patients who had such an event was 9•2 months (8•1–10•7) in the 90 mg group and 10•2 months (7•3–14•0) in the 30 mg group (p=0•63). In a retrospective analysis, eight patients in the pamidronate 90 mg group developed osteonecrosis of the jaw compared with two patients in the 30 mg group.
Interpretation: Monthly infusion of pamidronate 30 mg should be the recommended dose for prevention of bone disease in patients with multiple myeloma.
Supplementary editorial provided by OncologySTAT: In this phase III double-blinded, randomized study low-dose pamidronate were as effective as the higher dose and was associated with lower incidence of osteonecrosis of the jaw.
Discuss this dosing information with your oncologist. Ask for a dose of 30 mg or less.
Feel good and keep smiling! Pat