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.
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.


RESULTS
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.


CONCLUSIONS
Monthly infusion of pamidronate 30 mg should be the recommended dose for prevention of bone disease in patients with multiple myeloma.


BACKGROUND
Nordic Cancer Union and Novartis Healthcare.
Gimsing
Peter
P
Department of Haematology, Rigshospitalet and Copenhagen University, Copenhagen, Denmark. peter.gimsing@rh.regionH.dk
Carlson
Kristina
K
Turesson
Ingemar
I
Fayers
Peter
P
Waage
Anders
A
Vangsted
Annette
A
Mylin
Anne
A
Gluud
Christian
C
Juliusson
Gunnar
G
Gregersen
Henrik
H
Hjorth-Hansen
Henrik
H
Nesthus
Ingerid
I
Dahl
Inger Marie S
IM
Westin
Jan
J
Nielsen
Johan Lanng
JL
Knudsen
Lene Meldgaard
LM
Ahlberg
Lucia
L
Hjorth
Martin
M
Abildgaard
Niels
N
Andersen
Niels Frost
NF
Linder
Olle
O
Wisløff
Finn
F
D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001847:Bone Diseases / Q000000981:diagnostic imaging / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D004164:Diphosphonates / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007571:Jaw Diseases / Q000139:chemically induced; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D010020:Osteonecrosis / Q000139:chemically induced; D000077268:Pamidronate; D016016:Proportional Hazards Models; D011788:Quality of Life; D011859:Radiography; D018570:Risk Assessment; D012307:Risk Factors; D012537:Scandinavian and Nordic Countries; D033581:Stem Cell Transplantation; D013997:Time Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D000077268:Pamidronate