A Meta-analysis of the Antitumor Effect and Safety of Bisphosphonates in the Treatment of Multiple Myeloma

Overview

Journal Int J Clin Exp Med

Specialty General Medicine

Date 2015 Jul 30

PMID 26221212

Citations 5

Authors

Xiaoxue Wang

Xiaojing Yan

Yan Li

Affiliations

Soon will be listed here.

Abstract

Background: The objective of this meta-analysis was to determine the effectiveness and safety of bisphosphonates (BPs) for patients with multiple myeloma (MM).

Methods: The study included patients with MM, who were randomly allocated to receive either BPs or control. PubMed/Medline, Embase, the Cochrane Database of Systematic Reviews (CDSR), and the Cochrane Central Register of Controlled Trials were searched up to January 2014, and only published trials were included in the analysis. There was no language restriction. The results were analyzed using RevMan 5.2 software, which was provided by Cochrane Collaboration.

Results: Six randomized controlled trials (RCTs) covering 1951 patients with MM were included in the analysis. The clodronate subgroup showed superior progression-free survival compared to the other groups. The pooled hazard ratio (HR) was 0.57 [95% confidence interval (CI) 0.33-0.99, P = 0.04]. Regarding overall survival (OS), only zoledronic acid showed a clear advantage (HR = 0.51, 95% CI 0.33-0.77, P = 0.002) All BPs were effective at reducing skeletal-related events (SREs). The pooled risk ratios for the outcome of SREs were 0.72 (95% CI: 0.62-0.84, P < 0.0001) for the clodronate subgroup, 0.66 (95% CI: 0.48-0.91, P = 0.007) for the pamidronate subgroup, and 0.65 (95% CI: 0.46-0.91, P = 0.01) for the zoledronic acid subgroup. Several adverse events (AEs) were mentioned in the included RCTs; however, the pooled results showed no statistically significant differences between the BP groups and the control.

Conclusions: The present meta-analysis demonstrated that zoledronic acid may improve the OS of patients with MM. All BPs markedly decreased SREs and were tolerated well.

Citing Articles

Multiple myeloma masquerading as mandibular medication-related osteonecrosis of the jaw: a case report.

Danskin Y, Alhajji D, Singh A, Rota A, Huryn J, Estilo C Aust Dent J. 2021; 67(1):94-99.

PMID: 34706097 PMC: 9502029. DOI: 10.1111/adj.12882.

The Importance of Alliance between Hematologists and Dentists: A Retrospective Study on the Development of Bisphosphonates Osteonecrosis of the Jaws (Bronj) in Multiple Myeloma Patients.

Bacci C, Cerrato A, Dotto V, Zambello R, Barila G, Lico A Dent J (Basel). 2021; 9(2).

PMID: 33498207 PMC: 7908966. DOI: 10.3390/dj9020011.

Inhibitory effects of CP on the growth of human gastric adenocarcinoma BGC-823 tumours in nude mice.

Wang H, Liu Y, Zhou B, Zhang Z, Li A, An R J Int Med Res. 2018; 46(5):1756-1766.

PMID: 29569987 PMC: 5991239. DOI: 10.1177/0300060518761505.

Multiple myeloma presenting with bilateral ankle pain (microangiopathy) and complicated by streptococcal meningitis and Pneumocystis carinii pneumonia.

Dunphy L, Singh N, Keating E BMJ Case Rep. 2017; 2017.

PMID: 28174184 PMC: 5307268. DOI: 10.1136/bcr-2016-217289.

Bone marrow micro-environment is a crucial player for myelomagenesis and disease progression.

Mondello P, Cuzzocrea S, Navarra M, Mian M Oncotarget. 2017; 8(12):20394-20409.

PMID: 28099912 PMC: 5386771. DOI: 10.18632/oncotarget.14610.

References

Coleman R, de Boer R, Eidtmann H, Llombart A, Davidson N, Neven P . Zoledronic acid (zoledronate) for postmenopausal women with early breast cancer receiving adjuvant letrozole (ZO-FAST study): final 60-month results. Ann Oncol. 2012; 24(2):398-405. DOI: 10.1093/annonc/mds277. View

Lahtinen R, Laakso M, PALVA I, Virkkunen P, Elomaa I . Randomised, placebo-controlled multicentre trial of clodronate in multiple myeloma. Finnish Leukaemia Group. Lancet. 1992; 340(8827):1049-52. DOI: 10.1016/0140-6736(92)93075-x. View

Tierney J, Stewart L, Ghersi D, Burdett S, Sydes M . Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 2007; 8:16. PMC: 1920534. DOI: 10.1186/1745-6215-8-16. View

McCloskey E, MacLennan I, Drayson M, Chapman C, Dunn J, Kanis J . A randomized trial of the effect of clodronate on skeletal morbidity in multiple myeloma. MRC Working Party on Leukaemia in Adults. Br J Haematol. 1998; 100(2):317-25. DOI: 10.1046/j.1365-2141.1998.00567.x. View

Zou Y, Sheng Z, Lu H, Yu J . Continuous treatment with new agents for newly diagnosed multiple myeloma. Anticancer Drugs. 2013; 24(5):527-33. DOI: 10.1097/CAD.0b013e32836032d5. View

Powles T, Paterson A, McCloskey E, Schein P, Scheffler B, Tidy A . Reduction in bone relapse and improved survival with oral clodronate for adjuvant treatment of operable breast cancer [ISRCTN83688026]. Breast Cancer Res. 2006; 8(2):R13. PMC: 1557723. DOI: 10.1186/bcr1384. View

Gnant M, Mlineritsch B, Stoeger H, Luschin-Ebengreuth G, Heck D, Menzel C . Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 62-month follow-up from the ABCSG-12 randomised trial. Lancet Oncol. 2011; 12(7):631-41. DOI: 10.1016/S1470-2045(11)70122-X. View

Zarogoulidis K, Boutsikou E, Zarogoulidis P, Eleftheriadou E, Kontakiotis T, Lithoxopoulou H . The impact of zoledronic acid therapy in survival of lung cancer patients with bone metastasis. Int J Cancer. 2009; 125(7):1705-9. DOI: 10.1002/ijc.24470. View

Eidtmann H, de Boer R, Bundred N, Llombart-Cussac A, Davidson N, Neven P . Efficacy of zoledronic acid in postmenopausal women with early breast cancer receiving adjuvant letrozole: 36-month results of the ZO-FAST Study. Ann Oncol. 2010; 21(11):2188-2194. DOI: 10.1093/annonc/mdq217. View

10.

Morgan G, Davies F, Gregory W, Cocks K, Bell S, Szubert A . First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial. Lancet. 2010; 376(9757):1989-99. PMC: 3639680. DOI: 10.1016/S0140-6736(10)62051-X. View

11.

DArena G, Gobbi P, Broglia C, Sacchi S, Quarta G, Baldini L . Pamidronate versus observation in asymptomatic myeloma: final results with long-term follow-up of a randomized study. Leuk Lymphoma. 2011; 52(5):771-5. DOI: 10.3109/10428194.2011.553000. View

12.

Aviles A, Nambo M, Neri N, Castaneda C, Cleto S, Huerta-Guzman J . Antitumor effect of zoledronic acid in previously untreated patients with multiple myeloma. Med Oncol. 2007; 24(2):227-30. DOI: 10.1007/BF02698044. View

13.

Musto P, Petrucci M, Bringhen S, Guglielmelli T, Caravita T, Bongarzoni V . A multicenter, randomized clinical trial comparing zoledronic acid versus observation in patients with asymptomatic myeloma. Cancer. 2008; 113(7):1588-95. DOI: 10.1002/cncr.23783. View

14.

Martin A, Garcia-Sanz R, Hernandez J, Blade J, Suquia B, Fernandez-Calvo J . Pamidronate induces bone formation in patients with smouldering or indolent myeloma, with no significant anti-tumour effect. Br J Haematol. 2002; 118(1):239-42. DOI: 10.1046/j.1365-2141.2002.03549.x. View

15.

Aviles A, Neri N, Huerta-Guzman J, Nambo M . Randomized clinical trial of zoledronic acid in multiple myeloma patients undergoing high-dose chemotherapy and stem-cell transplantation. Curr Oncol. 2013; 20(1):e13-20. PMC: 3557337. DOI: 10.3747/co.20.1055. View

16.

Modi N, Lentzsch S . Bisphosphonates as antimyeloma drugs. Leukemia. 2011; 26(4):589-94. PMC: 3364444. DOI: 10.1038/leu.2011.282. View

17.

Gnant M, Mlineritsch B, Schippinger W, Luschin-Ebengreuth G, Postlberger S, Menzel C . Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Engl J Med. 2009; 360(7):679-91. DOI: 10.1056/NEJMoa0806285. View

18.

Berenson J, Lichtenstein A, Porter L, Dimopoulos M, Bordoni R, George S . Long-term pamidronate treatment of advanced multiple myeloma patients reduces skeletal events. Myeloma Aredia Study Group. J Clin Oncol. 1998; 16(2):593-602. DOI: 10.1200/JCO.1998.16.2.593. View

19.

Aft R, Naughton M, Trinkaus K, Weilbaecher K . Effect of (Neo)adjuvant zoledronic acid on disease-free and overall survival in clinical stage II/III breast cancer. Br J Cancer. 2012; 107(1):7-11. PMC: 3389411. DOI: 10.1038/bjc.2012.210. View

20.

Diel I, Jaschke A, Solomayer E, Gollan C, Bastert G, Sohn C . Adjuvant oral clodronate improves the overall survival of primary breast cancer patients with micrometastases to the bone marrow: a long-term follow-up. Ann Oncol. 2008; 19(12):2007-11. PMC: 2733118. DOI: 10.1093/annonc/mdn429. View