title: 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.
  
  
  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.
authors.affiliation: Department of Haematology, Rigshospitalet and Copenhagen University, Copenhagen, Denmark. peter.gimsing@rh.regionH.dk
authors.forename: Peter
authors.initials: P
authors.lastname: Gimsing
authors.forename: Kristina
authors.initials: K
authors.lastname: Carlson
authors.forename: Ingemar
authors.initials: I
authors.lastname: Turesson
authors.forename: Peter
authors.initials: P
authors.lastname: Fayers
authors.forename: Anders
authors.initials: A
authors.lastname: Waage
authors.forename: Annette
authors.initials: A
authors.lastname: Vangsted
authors.forename: Anne
authors.initials: A
authors.lastname: Mylin
authors.forename: Christian
authors.initials: C
authors.lastname: Gluud
authors.forename: Gunnar
authors.initials: G
authors.lastname: Juliusson
authors.forename: Henrik
authors.initials: H
authors.lastname: Gregersen
authors.forename: Henrik
authors.initials: H
authors.lastname: Hjorth-Hansen
authors.forename: Ingerid
authors.initials: I
authors.lastname: Nesthus
authors.forename: Inger Marie S
authors.initials: IM
authors.lastname: Dahl
authors.forename: Jan
authors.initials: J
authors.lastname: Westin
authors.forename: Johan Lanng
authors.initials: JL
authors.lastname: Nielsen
authors.forename: Lene Meldgaard
authors.initials: LM
authors.lastname: Knudsen
authors.forename: Lucia
authors.initials: L
authors.lastname: Ahlberg
authors.forename: Martin
authors.initials: M
authors.lastname: Hjorth
authors.forename: Niels
authors.initials: N
authors.lastname: Abildgaard
authors.forename: Niels Frost
authors.initials: NF
authors.lastname: Andersen
authors.forename: Olle
authors.initials: O
authors.lastname: Linder
authors.forename: Finn
authors.initials: F
authors.lastname: Wisløff
mesh_terms: 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
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D000077268:Pamidronate