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

Clive AO, Hooper CE, Edey AJ, Morley AJ, Zahan-Evans N, Hall D, Lyburn I, White P, Braybrooke JP, Sequeiros I, Lyen SM, Milton T, Kahan BC, Maskell NA - PLoS ONE (2015)

Bottom Line: We performed a pilot study to evaluate its effects in humans.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.Although no convincing treatment effect was identified, potential benefits for specific subgroups of patients cannot be excluded.

View Article: PubMed Central - PubMed

Affiliation: Academic Respiratory Unit, University of Bristol, Bristol, United Kingdom; North Bristol Lung Centre, Southmead Hospital, North Bristol NHS Trust, Bristol, United Kingdom.

ABSTRACT

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 www.isrctn.com.

No MeSH data available.


Related in: MedlinePlus

Box and whisper plot showing the change in blood biomarkers over time for the 2 treatment arms.The horizontal line with the box represents the median. The box edges represent the lower (25th) and upper (75th) quartiles. The whiskers represent the lower and upper adjacent values. Outside values are plotted separately.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4364455&req=5

pone.0118569.g005: Box and whisper plot showing the change in blood biomarkers over time for the 2 treatment arms.The horizontal line with the box represents the median. The box edges represent the lower (25th) and upper (75th) quartiles. The whiskers represent the lower and upper adjacent values. Outside values are plotted separately.

Mentions: Evaluating the changes in serum biomarkers over time (mesothelin, serum VEGF, NLR, IL6 and MCP-1) there was no difference seen between the treatment arms (see Fig. 5 and online S3 File).


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

Clive AO, Hooper CE, Edey AJ, Morley AJ, Zahan-Evans N, Hall D, Lyburn I, White P, Braybrooke JP, Sequeiros I, Lyen SM, Milton T, Kahan BC, Maskell NA - PLoS ONE (2015)

Box and whisper plot showing the change in blood biomarkers over time for the 2 treatment arms.The horizontal line with the box represents the median. The box edges represent the lower (25th) and upper (75th) quartiles. The whiskers represent the lower and upper adjacent values. Outside values are plotted separately.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4364455&req=5

pone.0118569.g005: Box and whisper plot showing the change in blood biomarkers over time for the 2 treatment arms.The horizontal line with the box represents the median. The box edges represent the lower (25th) and upper (75th) quartiles. The whiskers represent the lower and upper adjacent values. Outside values are plotted separately.
Mentions: Evaluating the changes in serum biomarkers over time (mesothelin, serum VEGF, NLR, IL6 and MCP-1) there was no difference seen between the treatment arms (see Fig. 5 and online S3 File).

Bottom Line: We performed a pilot study to evaluate its effects in humans.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.Although no convincing treatment effect was identified, potential benefits for specific subgroups of patients cannot be excluded.

View Article: PubMed Central - PubMed

Affiliation: Academic Respiratory Unit, University of Bristol, Bristol, United Kingdom; North Bristol Lung Centre, Southmead Hospital, North Bristol NHS Trust, Bristol, United Kingdom.

ABSTRACT

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 www.isrctn.com.

No MeSH data available.


Related in: MedlinePlus