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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Meta-analysis on the effects of octreotide on tumor mass in acromegaly

A Giustina, G Mazziotti, V Torri, M Spinello, I Floriani, and S Melmed.

Review published: 2012.

CRD summary

The authors concluded that octreotide was associated with clinically relevant tumour shrinkage in over half of patients with acromegaly. Limitations relating to the reliability of included study results and to the wide variation in results across studies suggests the authors' conclusions may not be reliable.

Authors' objectives

To examine the effectiveness of octreotide for tumour shrinkage in acromegaly.

Searching

MEDLINE and EMBASE was searched up to November 2010; search terms were reported. References from included studies and reviews were checked for additional studies. No limits on language of publications were applied.

Study selection

Randomised and non-randomised studies of patients with acromegaly who received octreotide, with data on tumour shrinkage, were eligible for inclusion. Studies that included mixed cohorts that received either octreotide or lanreotide were excluded. In addition, studies were required to provide a clear definition of clinically important reduction in tumour size.

Mean/median age ranged from 40 to 55 years. Approximately half of included studies included only treatment-naive patients. Most other studies included a combination of those who had received radiotherapy, somatostatin analogues or were treatment native patients. Approximately half of studies used subcutaneous octreotide and the rest used intramuscular long acting repeatable (LAR) octreotide. Doses varied widely. Most studies used magnetic resonance imaging (MRI) to examine tumour shrinkage, although a substantial number also used both computerized tomography (CT) and MRI. Definition of tumour shrinkage differed between studies ranging from 10% to 30% reduction in size or volume and 1mm to 3mm reduction in diameter. Duration of treatment ranged from two weeks to 30 months

Two reviewers independently selected studies for inclusion with any differences resolved through discussion.

Assessment of study quality

The authors did not state explicitly if they critically appraised studies. However, information related to study design (randomised or non-randomised, prospective or retrospective) and blinding (sometimes) was reported.

Data extraction

Outcomes (percentage tumour shrinkage, mean percentage reduction from baseline in tumour size) were extracted from studies to calculate a percentage or percentage reduction, and 95% confidence intervals (CI), of patients who experienced tumour shrinkage.

Two reviewers independently extracted data with any differences resolved through discussion with a third reviewer.

Methods of synthesis

Outcomes on percentage tumour shrinkage and percentage change were pooled from the included studies using a random-effects model. Heterogeneity was assessed using the Q and Ι² statistics.

Sensitivity analyses were conducted to assess the impact of using different measurement of shrinkage (linear versus volumetric), more stringent criteria for shrinkage (volume decrease 20% or more) or assessing shrinkage by MRI. Predictors of response were examined using Χ². Potential publication bias was investigated using funnel plots and Egger's test.

Results of the review

Forty-one studies were included in the review (1,685 patients). Five studies were retrospective, the rest used a prospective design. Although there were 11 comparative trials, results of comparisons between octreotide and controls were not examined. Double-blinding was reported for only one trial.

There was tumour shrinkage in 53% of patients (95% CI 45 to 61; Ι²=90%), but with very high heterogeneity. This estimate was a little higher when only using MRI (60%; 95% CI 51 to 70) or using more stringent criteria for shrinkage (57%; 95% CI 47 to 67).The mean percentage reduction in tumour size was 37.4% (95% CI 22.4 to 52.4; nine studies).

Higher tumour shrinkage estimates were found in studies that investigated tumour volume rather than linear measurements (OR 2.73; 95% CI 1.73 to 4.31). Estimates were also higher in those treated with intramuscular long acting repeatable (LAR) octreotide rather than subcutaneously (OR 3.18; 95% CI 1.95 to 5.20). There was also higher reported shrinkage in patients receiving treatment for more than a year compared with those receiving for less than a year (OR 1.90; 95% CI 1.02 to 3.55). Studies with a higher proportion of treatment naive patients also found higher shrinkage estimates (test for trend: p<.001). Studies with a higher proportion of patients with safe growth hormone levels found higher shrinkage (test for trend: p<.001).

There was no evidence to indicate publication bias.

Authors' conclusions

Octreotide was associated with clinically important tumour shrinkage in over half of patients with acromegaly.

CRD commentary

The review question and inclusion criteria were clear. An adequate search of relevant sources was undertaken. Language restrictions were not applied which reduced risk of language bias. However, there was no indication that unpublished material was sought. Appropriate methods were used to minimise error and bias in study selection and data extraction. However, a very limited quality assessment was conducted.

Study details were adequately provided for all studies. Important limitations were identified including that most were non-comparative, open label and had a small sample size. Shrinkage estimates were based on end point data without reference to a comparator so werevulnerable to confounding. There was also very high heterogeneity which raised doubts on the validity of pooled estimates. There were 11 trials that included comparators (nine randomised trials) so it was unclear why no comparative analyses were evaluated in the systematic review. The authors acknowledge limitations of included studies, but their conclusions did not appear to adequately reflect these limitations.

Meta-analyses of non-comparative analyses with high heterogeneity, and included studies of limited quality, suggest the authors' conclusions may not be reliable.

Implications of the review for practice and research

Practice: The authors did not state any implications for practice

Research: The authors stated further research should investigate how somatostatin receptor subtypes may mediate antimitotic effects.

Funding

Novartis.

Bibliographic details

Giustina A, Mazziotti G, Torri V, Spinello M, Floriani I, Melmed S. Meta-analysis on the effects of octreotide on tumor mass in acromegaly. PLOS ONE 2012; 7(5): 36411. [PMC free article: PMC3344864] [PubMed: 22574156]

Indexing Status

Subject indexing assigned by NLM

MeSH

Acromegaly /complications /drug therapy; Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents /pharmacology /therapeutic use; Clinical Trials as Topic; Female; Humans; Male; Middle Aged; Octreotide /pharmacology /therapeutic use; Pituitary Neoplasms /complications /drug therapy /pathology; Tumor Burden /drug effects; Young Adult

AccessionNumber

12012025525

Database entry date

06/12/2012

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 22574156

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