Pasireotide (SOM230) demonstrates efficacy and safety in patients with acromegaly: a randomized, multicenter, phase II trial.
BACKGROUND
Pasireotide (SOM230) is a novel multireceptor ligand somatostatin analog with affinity for somatostatin receptor subtypes sst(1-3) and sst(5). Because most GH-secreting pituitary adenomas express sst(2) and sst(5), pasireotide has the potential to be more effective than the sst(2)-preferential somatostatin analogs octreotide and lanreotide.


OBJECTIVE
Our objective was to evaluate the efficacy and safety of three different doses of pasireotide in patients with acromegaly.


METHODS
We conducted a phase II, randomized, multicenter, open-label, three-way, crossover study.


METHODS
Sixty patients with acromegaly, defined by a 2-h five-point mean GH level higher than 5 microg/liter, lack of suppression of GH to less than 1 microg/liter after oral glucose tolerance test, and elevated IGF-I for age- and sex-matched controls. Patients could have had previous surgery, radiotherapy, and/or medical therapy or no previous treatment.


METHODS
After treatment with octreotide 100 microg s.c. three times daily for 28 d, each patient received pasireotide 200, 400, and 600 microg s.c. twice daily in random order for 28 d.


METHODS
A biochemical response was defined as a reduction in GH to no more than 2.5 microg/liter and normalization of IGF-I to age- and sex-matched controls.


RESULTS
After 4 wk of octreotide, 9% of patients achieved a biochemical response. After 4 wk of pasireotide 200-600 microg s.c. bid, 19% of patients achieved a biochemical response, which increased to 27% after 3 months of pasireotide; 39% of patients had a more than 20% reduction in pituitary tumor volume. Pasireotide was generally well tolerated.


CONCLUSIONS
Pasireotide is a promising treatment for acromegaly. Larger studies of longer duration evaluating the efficacy and safety of pasireotide in patients with acromegaly are ongoing.
Petersenn
S
S
Division of Endocrinology, Medical Center, University of Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany. stephan.petersenn@uni-due.de
Schopohl
J
J
Barkan
A
A
Mohideen
P
P
Colao
A
A
Abs
R
R
Buchelt
A
A
Ho
Y-Y
YY
Hu
K
K
Farrall
A J
AJ
Melmed
S
S
Biller
B M K
BM
D000172:Acromegaly / Q000188:drug therapy*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000378:metabolism; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D023381:Endpoint Determination; D005260:Female; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000009:adverse effects / Q000627:therapeutic use; D010911:Pituitary Neoplasms / Q000473:pathology; D013004:Somatostatin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D055815:Young Adult
D001786:Blood Glucose; D019382:Human Growth Hormone; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; C517782:pasireotide; D015282:Octreotide