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Submitted on February 7, 2005
Accepted on May 4, 2005
Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, NY, Departments of Neurosurgery and Medicine, Stanford University Medical Center, Stanford, CA, Department of Internal Medicine, Erasmus MC, The Netherlands, Department of Statistics, Columbia University, New York, NY
* To whom correspondence should be addressed. E-mail: puf1{at}columbia.edu.
Context: Although considerable data exist on the use of long-acting somatostatin analogs to treat acromegaly their reported efficacy differs substantially among trials.
Objective: We conducted a meta-analysis to derive definitive estimates of their efficacy for biochemical control and tumor shrinkage.
Data Sources: A search of literature through 2003, primarily via Pub-med.
Study Selection: Inclusion criteria, met in 44 trials, included 
3 months of secondary octreotide LAR or lanreotide SR therapy or of primary octreotide LAR, lanreotide SR, or sc octreotide therapy and clearly reported data on biochemical efficacy and/or tumor shrinkage. Fifty other trials screened did not meet analysis inclusion criteria.
Data Extraction: Data were extracted by 3 independent observers.
Data Synthesis: Among subjects not selected for somatostatin analog responsiveness before study entry, both GH efficacy criteria and IGF-I normalization were met in a greater proportion of those treated with octreotide LAR vs. lanreotide SR (GH: B=0.2310, P = 0.016; IGF-I: B=0.2325, P = 0.007). Pre-study selection for somatostatin analog responsiveness was not a significant predictor of meeting GH efficacy criteria (B=0.0992, P = 0.12). Pre-selection was a positive predictor of IGF-I normalization rate (B = 0.1213, P = 0.04), which was greater among pre-selected than unselected subjects (B=0.1472, P = 0.0475). IGF-I normalization occurred in a greater proportion of secondary octreotide LAR vs. primary octreotide treated subjects (B= .2056, P = 0.009).
The odds of tumor shrinkage more than 10% were lower in the unselected vs. pre-selected subjects. However, the effect of drug type was an important predictor of shrinkage such that regardless of pre-selection or not, the odds of shrinkage with lanreotide SR was lower than with octreotide LAR (P = 0.003). Shrinkage > 10% occurred in a greater percentage of primary octreotide LAR vs. primary octreotide sc treated subjects; OR = 9.4, P < 0.0001. The overall rate of tumor increase was 1.4%.
Conclusions: In this meta-analysis we have shown that the efficacy of octreotide LAR is greater than lanreotide SR among subjects unselected for prior somatostatin analog responsiveness. Pre-selection is a significant positive predictor of IGF-I normalization and is associated with increased odds of tumor shrinkage, which is also greatest with octreotide LAR. Biochemical efficacy is similar, but tumor shrinkage is greater when these drugs are given as primary vs. secondary therapy.
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