Long-acting somatostatin analog therapy of acromegaly: a meta-analysis.
BACKGROUND
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.


METHODS
A search of literature was conducted through 2003, primarily via PubMed.


METHODS
Inclusion criteria, met in 44 trials, included at least 3 months of secondary octreotide long-acting release (LAR) or lanreotide slow release (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.


METHODS
Data were extracted by three independent observers.


RESULTS
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). Prestudy selection for somatostatin analog responsiveness was not a significant predictor of meeting GH efficacy criteria (B = 0.0992; P = 0.12). Preselection was a positive predictor of IGF-I normalization rate (B = 0.1213; P = 0.04), which was greater among preselected 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 = 0.2056; P = 0.009). The odds of tumor shrinkage more than 10% were lower in the unselected vs. preselected subjects. However, the effect of drug type was an important predictor of shrinkage; such that regardless of preselection or not, the odds of shrinkage with lanreotide SR were lower than with octreotide LAR (P = 0.003). Shrinkage greater than 10% occurred in a higher percentage of primary octreotide LAR-treated vs. primary octreotide sc-treated subjects (odds ratio = 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. Preselection 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.
Freda
Pamela U
PU
Department of Medicine, Columbia University, College of Physicians and Surgeons, 630 West 168th Street, New York, New York 10032, USA. puf1@columbia.edu
Katznelson
Laurence
L
van der Lely
Aart Jan
AJ
Reyes
Carlos M
CM
Zhao
Shouhao
S
Rabinowitz
Daniel
D
D000172:Acromegaly / Q000188:drug therapy*; D000970:Antineoplastic Agents / Q000008:administration & dosage; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D006801:Humans; D015282:Octreotide / Q000008:administration & dosage*; D010456:Peptides, Cyclic / Q000008:administration & dosage; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives*
D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin; D015282:Octreotide