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

Peter Gimsing, Kristina Carlson, Ingemar Turesson, Peter Fayers, Anders Waage, Annette Juul Vangsted, Anne Kærsgaard Mylin, Christian Nyfeldt Gluud, Gunnar Juliusson, Henrik Gregersen, Henrik Hjorth-Hansen, Ingerid Nesthus, Inger Marie Dahl Bahn, Jan Westin, Johan Lanng Nielsen, Lene Meldgaard Knudsen, Lucia Ahlberg, Martin Hjorth, Niels Abildgaard, Olle LinderFinn Wisløff

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.
OriginalsprogEngelsk
TidsskriftLancet Oncology
Vol/bind11
Udgave nummer10
Sider (fra-til)973-82
Antal sider10
ISSN1470-2045
DOI
StatusUdgivet - 1. okt. 2010

Fingeraftryk

Randomized Controlled Trials
Denmark
Norway
Random Allocation
Intravenous Infusions
Placebos
Quality of Life
Delivery of Health Care
Neoplasms

Citer dette

Gimsing, Peter ; Carlson, Kristina ; Turesson, Ingemar ; Fayers, Peter ; Waage, Anders ; Vangsted, Annette Juul ; Mylin, Anne Kærsgaard ; Gluud, Christian Nyfeldt ; Juliusson, Gunnar ; Gregersen, Henrik ; Hjorth-Hansen, Henrik ; Nesthus, Ingerid ; Bahn, Inger Marie Dahl ; Westin, Jan ; Nielsen, Johan Lanng ; Meldgaard Knudsen, Lene ; Ahlberg, Lucia ; Hjorth, Martin ; Abildgaard, Niels ; Linder, Olle ; Wisløff, Finn. / 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. I: Lancet Oncology. 2010 ; Bind 11, Nr. 10. s. 973-82.
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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. 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.",
author = "Peter Gimsing and Kristina Carlson and Ingemar Turesson and Peter Fayers and Anders Waage and Vangsted, {Annette Juul} and Mylin, {Anne K{\ae}rsgaard} and Gluud, {Christian Nyfeldt} and Gunnar Juliusson and Henrik Gregersen and Henrik Hjorth-Hansen and Ingerid Nesthus and Bahn, {Inger Marie Dahl} and Jan Westin and Nielsen, {Johan Lanng} and {Meldgaard Knudsen}, Lene and Lucia Ahlberg and Martin Hjorth and Niels Abildgaard and Olle Linder and Finn Wisl{\o}ff",
note = "Copyright {\circledC} 2010 Elsevier Ltd. All rights reserved.",
year = "2010",
month = "10",
day = "1",
doi = "10.1016/S1470-2045(10)70198-4",
language = "English",
volume = "11",
pages = "973--82",
journal = "The Lancet Oncology",
issn = "1470-2045",
publisher = "TheLancet Publishing Group",
number = "10",

}

Gimsing, P, Carlson, K, Turesson, I, Fayers, P, Waage, A, Vangsted, AJ, Mylin, AK, Gluud, CN, Juliusson, G, Gregersen, H, Hjorth-Hansen, H, Nesthus, I, Bahn, IMD, Westin, J, Nielsen, JL, Meldgaard Knudsen, L, Ahlberg, L, Hjorth, M, Abildgaard, N, Linder, O & Wisløff, F 2010, '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 Oncology, bind 11, nr. 10, s. 973-82. https://doi.org/10.1016/S1470-2045(10)70198-4

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. / Gimsing, Peter; Carlson, Kristina; Turesson, Ingemar; Fayers, Peter; Waage, Anders; Vangsted, Annette Juul; Mylin, Anne Kærsgaard; Gluud, Christian Nyfeldt; Juliusson, Gunnar; Gregersen, Henrik; Hjorth-Hansen, Henrik; Nesthus, Ingerid; Bahn, Inger Marie Dahl; Westin, Jan; Nielsen, Johan Lanng; Meldgaard Knudsen, Lene; Ahlberg, Lucia; Hjorth, Martin; Abildgaard, Niels; Linder, Olle; Wisløff, Finn.

I: Lancet Oncology, Bind 11, Nr. 10, 01.10.2010, s. 973-82.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - 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

AU - Gimsing, Peter

AU - Carlson, Kristina

AU - Turesson, Ingemar

AU - Fayers, Peter

AU - Waage, Anders

AU - Vangsted, Annette Juul

AU - Mylin, Anne Kærsgaard

AU - Gluud, Christian Nyfeldt

AU - Juliusson, Gunnar

AU - Gregersen, Henrik

AU - Hjorth-Hansen, Henrik

AU - Nesthus, Ingerid

AU - Bahn, Inger Marie Dahl

AU - Westin, Jan

AU - Nielsen, Johan Lanng

AU - Meldgaard Knudsen, Lene

AU - Ahlberg, Lucia

AU - Hjorth, Martin

AU - Abildgaard, Niels

AU - Linder, Olle

AU - Wisløff, Finn

N1 - Copyright © 2010 Elsevier Ltd. All rights reserved.

PY - 2010/10/1

Y1 - 2010/10/1

N2 - 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.

AB - 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.

U2 - 10.1016/S1470-2045(10)70198-4

DO - 10.1016/S1470-2045(10)70198-4

M3 - Journal article

C2 - 20863761

VL - 11

SP - 973

EP - 982

JO - The Lancet Oncology

JF - The Lancet Oncology

SN - 1470-2045

IS - 10

ER -