Antiproliferative effect of the somatostatin analogue octreotide on growth hormone-producing pituitary tumors: results of a multicenter randomized trial.
OBJECTIVE
To determine and quantify the in vivo effects of octreotide on the cell cycle kinetics of growth hormone-producing pituitary adenomas.


METHODS
A multicenter randomized trial had been conducted to assess the clinical efficacy of octreotide, and we studied tissue specimens from pituitary macroadenomas in 32 patients with acromegaly from that trial-16 of whom had received 4 months of octreotide therapy before surgical resection and 16 of whom had undergone surgical resection only.


METHODS
All tumors had been fully characterized on the basis of their immunophenotypic profile and their ultrastructural morphologic features. Included were 16 densely and 16 sparsely granulated somatotroph adenomas. In each case, immunostaining for the cell cycle-specific nuclear antigen Ki-67 was performed with use of the MIB-1 antibody. The staining reaction was manually quantified, and a tumor growth fraction was derived in each case.


RESULTS
The mean growth fraction of tumors exposed to octreotide was suppressed by 83% in comparison with untreated surgical controls (0.011+/-0.004% versus 0.065+/-0.016%, respectively; P = 0.0068). The association between octreotide treatment and lower tumor growth fractions was statistically independent of tumor subtype, being evident among both sparsely and densely granulated somatotroph adenomas.


CONCLUSIONS
Octreotide exerts a significant antineoplastic effect on somatotroph adenomas, one readily reflected at the level of the cell cycle. This antiproliferative response provides insight into several clinicopathologic issues surrounding octreotide therapy for these neoplasms.
Thapar
K
K
Division of Neurosurgery, St. Michael's Hospital, University of Toronto, Ontario, Canada.
Kovacs
K T
KT
Stefaneanu
L
L
Scheithauer
B W
BW
Horvath
E
E
Lloyd
R V
RV
Li
J
J
Laws
E R
ER
D000172:Acromegaly / Q000209:etiology; D000236:Adenoma / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D005260:Female; D013006:Growth Hormone / Q000096:biosynthesis / Q000187:drug effects*; D006801:Humans; D019394:Ki-67 Antigen / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000627:therapeutic use*; D010911:Pituitary Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*
D018931:Antineoplastic Agents, Hormonal; D019394:Ki-67 Antigen; D013006:Growth Hormone; D015282:Octreotide