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.

Abstract

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.

FUNDING:

Nordic Cancer Union and Novartis Healthcare.

• Authors: Peter Gimsing, Kristina Carlson, Ingemar Turesson, Peter Fayers, Anders Waage, Annette Vangsted, Anne Mylin, Christian Gluud, Gunnar Juliusson, Henrik Gregersen, Henrik Hjorth-Hansen, Ingerid Nesthus, Inger Marie S Dahl, Jan Westin, Johan Lanng Nielsen, Lene Meldgaard Knudsen, Lucia Ahlberg, Martin Hjorth, Niels Abildgaard, Niels Frost Andersen, Olle Linder, Finn Wisløff
• Journal: The Lancet. Oncology (Lancet Oncol) Vol. 11 Issue 10 Pg. 973-82 (Oct 2010) ISSN: 1474-5488 [Electronic] England
• PMID: 20863761 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Bone Density Conservation Agents
• Diphosphonates
• Pamidronate

Topics

• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Bone Density Conservation Agents (administration & dosage, adverse effects)
• Bone Diseases (diagnostic imaging, etiology, mortality, prevention & control)
• Diphosphonates (administration & dosage, adverse effects)
• Double-Blind Method
• Female
• Humans
• Infusions, Intravenous
• Jaw Diseases (chemically induced)
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Multiple Myeloma (complications, diagnosis, mortality, therapy)
• Osteonecrosis (chemically induced)
• Pamidronate
• Proportional Hazards Models
• Quality of Life
• Radiography
• Risk Assessment
• Risk Factors
• Scandinavian and Nordic Countries
• Stem Cell Transplantation
• Time Factors
• Transplantation, Autologous
• Treatment Outcome