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A randomised controlled trial of intravenous zoledronic acid in malignant pleural disease: A proof of principle pilot study

Maskell, Nick A.; Kahan, Brennan C.; Lyen, Stephen M.; Sequeiros, Iara; Braybrooke, Jeremy P.; Morley, Anna J.; Edey, Anthony J.; Hooper, Clare E.; Clive, Amelia O.; Clive, Amelia O; Hooper, Clare E; Edey, Anthony J; Morley, Anna J; Zahan-Evans, Natalie; Hall, David; Lyburn, Iain; White, Paul; Braybrooke, Jeremy P; Sequerios, Iara; Lyen, Stephen M; Milton, Tim; Kahan, Brennan C; Maskell, Nick A


Nick A. Maskell

Brennan C. Kahan

Stephen M. Lyen

Iara Sequeiros

Jeremy P. Braybrooke

Anna J. Morley

Anthony J. Edey

Clare E. Hooper

Amelia O. Clive

Amelia O Clive

Clare E Hooper

Anthony J Edey

Anna J Morley

Natalie Zahan-Evans

David Hall

Iain Lyburn

Paul White
Professor in Applied Statistics

Jeremy P Braybrooke

Iara Sequerios

Stephen M Lyen

Tim Milton

Brennan C Kahan

Nick A Maskell


© 2015 Clive et al. Introduction: Animal studies have shown Zoledronic Acid (ZA) may diminish pleural fluid accumulation and tumour bulk in malignant pleural disease (MPD). We performed a pilot study to evaluate its effects in humans. Methods: We undertook a single centre, double-blind, placebo-controlled trial in adults with MPD. Patients were randomised (1:1) to receive 2 doses of intravenous ZA or placebo, 3 weeks apart and were followed-up for 6 weeks. The co-primary outcomes were change in Visual Analogue Scale (VAS) score measured breathlessness during trial follow-up and change in the initial area under the curve (iAUC) on thoracic Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) from randomisation to week 5. Multiple secondary endpoints were also evaluated. Results: Between January 2010 and May 2013, 30 patients were enrolled, 24 randomised and 4 withdrew after randomisation (1 withdrew consent; 3 had a clinical decline). At baseline, the ZA group were more breathless, had more advanced disease on radiology and worse quality of life than the placebo group. There was no significant difference between the groups with regards change in breathlessness (Adjusted mean difference (AMD) 4.16 (95%CI -4.7 to 13.0)) or change in DCE-MRI iAUC (AMD -15.4 (95%CI -58.1 to 27.3). Two of nine (22%) in the ZA arm had a >10% improvement by modified RECIST (vs 0/11 who received placebo). There was no significant difference in quality of life measured by the QLQ-C30 score (global QOL: AMD -4.1 (-13.0 to 4.9)), side effects or serious adverse event rates. Conclusions: This is the first human study to evaluate ZA in MPD. The study is limited by small numbers and imbalanced baseline characteristics. Although no convincing treatment effect was identified, potential benefits for specific subgroups of patients cannot be excluded. This study provides important information regarding the feasibility of future trials to evaluate the effects of ZA further. Trial Registration: UK Clinical Research Network ID 8877 ISRCTN17030426


Maskell, N. A., Kahan, B. C., Lyen, S. M., Sequeiros, I., Braybrooke, J. P., Morley, A. J., …Maskell, N. A. (2015). A randomised controlled trial of intravenous zoledronic acid in malignant pleural disease: A proof of principle pilot study. PLoS ONE, 10(3),

Journal Article Type Article
Publication Date Mar 17, 2015
Journal PLoS ONE
Electronic ISSN 1932-6203
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 10
Issue 3
Keywords intravenous zoledronic acid, pleural disease
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