帕米膦酸二钠 30mg 与 90mg 对初诊多发性骨髓瘤患者身体功能的影响（北欧骨髓瘤研究组）：一项双盲、随机对照试验。

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.

机构信息

Department of Haematology, Rigshospitalet and Copenhagen University, Copenhagen, Denmark.

出版信息

Lancet Oncol. 2010 Oct;11(10):973-82. doi: 10.1016/S1470-2045(10)70198-4.

DOI:10.1016/S1470-2045(10)70198-4

PMID:20863761

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.

摘要

背景

与安慰剂相比，双磷酸盐类药物的预防性治疗可降低多发性骨髓瘤患者发生骨骼事件的风险。然而，由于长期使用双磷酸盐类药物治疗相关的毒性，确定最低有效剂量很重要。本研究比较了两种剂量帕米膦酸二钠对新诊断多发性骨髓瘤患者健康相关生活质量和骨骼发病率的影响。

方法

这项双盲、随机、3 期临床试验在丹麦、挪威和瑞典的 37 家诊所进行。开始抗骨髓瘤治疗的多发性骨髓瘤患者以 1:1 的比例随机分配，接受每月一次静脉输注帕米膦酸二钠 30 毫克或 90 毫克，至少 3 年。随机分配使用中央计算机最小化系统进行。主要结局是欧洲癌症研究与治疗组织（EORTC）生活质量问卷（QLQ-C30）在 12 个月时评估的身体功能（范围 0-100）。所有在 12 个月时返回问卷且仍在接受研究治疗的患者均纳入主要终点分析。该研究在 ClinicalTrials.gov 注册，编号为 NCT00376883。

结果

从 2001 年 1 月至 2005 年 8 月，504 名患者被随机分配至帕米膦酸二钠 30 毫克或 90 毫克组（每组 252 名）。90 毫克组中有 157 名患者和 30 毫克组中有 156 名患者纳入主要分析。90 毫克组在 12 个月时的平均身体功能为 66 分（95%CI 62.9-70.0），30 毫克组为 68 分（95%CI 64.6-71.4）（95%CI 差值为-6.6 至 3.3；p=0.52）。90 毫克组中首次发生骨骼相关事件的患者中位时间为 9.2 个月（8.1-10.7），30 毫克组为 10.2 个月（7.3-14.0）（p=0.63）。在回顾性分析中，90 毫克帕米膦酸二钠组有 8 名患者发生颌骨坏死，而 30 毫克组有 2 名患者发生。