Efficacy of clodronate, pamidronate, and zoledronate in reducing morbidity and mortality in cancer patients with bone metastasis: a meta-analysis of randomized clinical trials.
BACKGROUND
Complications from skeletal-related events (SREs) constitute a challenge in the care of patients with metastatic bone disease (MBD) that originated from any type of malignancy.


OBJECTIVE
The purpose of this article was to compare the efficacy of clodronate, pamidronate, and zoledronate with that of placebo in reducing morbidity and overall mortality in cancer patients with MBD.


METHODS
MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched (from inception to January 2009) to retrieve randomized clinical trials that evaluated the bisphosphonates of interest. The search included articles published in English, French, Italian, Portugese, and Spanish. Patients with a definite (ie, biopsy-proven) diagnosis of MBD were included in the analysis. We extracted and combined data from studies that reported the number of patients with SREs and mortality data. A random-effects, meta-analytic model was applied in all calculations. The Jadad scale was used to assess the quality of study reporting.


RESULTS
The literature search identified 62 potential full-text studies; 44 of these studies were excluded and 18 were evaluated. The mean (SD) quality of reporting of the included studies was 57.8% (22.6%), or 2.89/5 (1.1/5). Each of the 3 drugs was found to be more effective than placebo in preventing all SREs in cancer patients with MBD. The relative risk of developing SREs was 0.70 (95% CI, 0.61-0.81; N = 1211) for zoledronate, 0.81 (95% CI, 0.73-0.91; N = 2251) for pamidronate, and 0.87 (95% CI, 0.75-1.00; N = 681) for clodronate. However, no clear advantage of one drug over the others was observed (CIs overlapped substantially). None of the bisphosphonates was more beneficial than placebo in reducing the number of deaths in the course of the trials (P = NS).


CONCLUSIONS
Clodronate, pamidronate, and zoled-ronate were associated with reductions in morbidity in cancer patients with MBD with regard to preventing SREs, but were not associated with a reduction in overall mortality.
Machado
Márcio
M
Toronto Health Economics and Technology Assessment Collaborative (THETA), University of Toronto, Toronto, Ontario, Canada. m.machado@utoronto.ca
Cruz
Lorena Souza
LS
Tannus
Gabriela
G
Fonseca
Marcelo
M
D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D004002:Clodronic Acid / Q000627:therapeutic use*; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D000077268:Pamidronate; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D016019:Survival Analysis; D016896:Treatment Outcome; D000077211:Zoledronic Acid
D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D004002:Clodronic Acid; D000077211:Zoledronic Acid; D000077268:Pamidronate