Preoperative lanreotide treatment for GH-secreting pituitary adenomas: effect on tumour volume and predictive factors of significant tumour shrinkage.
OBJECTIVE
The objective of this open study of 104 patients was to determine whether the somatostatin analogue lanreotide shrinks GH-secreting adenomas and to identify the predictive factors of a significant tumour volume reduction (> 20%).


METHODS
A total of 104 previously untreated and newly diagnosed acromegalic patients received the prolonged release (PR) formulation of lanreotide (lanreotide 30 mg, one intramuscular injection every 10 days) for either 1 (n = 84), 2 (n = 13), or 3 or more (n = 7) months before transsphenoidal surgery.


METHODS
Pituitary tumour volumes, tumour extension grade and possible cavernous sinus invasion were assessed in blinded conditions by a centralized team of radiologists. Factors such as demographics, tumour characteristics, GH and IGF-I levels were evaluated as possible predictive factors of a significant tumour volume reduction. The clinical activity and random GH, IGF-I, IGFBP-3, PRL, TSH, free T4 and lanreotide levels serum concentrations were measured under basal conditions and in the 10 days before surgery. All analyses were done in a centralized laboratory. The tolerability of preoperative PR lanreotide and the surgical outcome at the 6th month after surgery were assessed.


RESULTS
The presurgical treatment improved the symptoms of acromegaly and induced a statistically significant reduction of GH, IGF-I and IGFBP-3. Despite the short duration of the preoperative lanreotide 30 mg treatment, IGF-I levels were normalized in 25% of patients. A statistically significant reduction in tumour volume (P < 0.001) was observed. The median value of the differences was -152 mm3. A reduction in tumour volume was observed in 66% of patients and was > 20% in 29% of all patients included. Both the univariate analyses and the logistic regression model demonstrated that a positive hormone response to preoperative lanreotide 30 mg was the sole predictive factor of a significant tumour shrinkage (odds ratio of 7.8, 95% confidence interval 1.6-37.1). Preoperative PR lanreotide did not modify the expected soft consistence of the tumour. The main adverse events consisted of minor gastrointestinal problems. Univariate analyses revealed that younger age, higher GH and IGF-I levels at diagnosis, higher preoperative tumour volume, more than one tumour extrasellar extension and the presence of cavernous sinus invasion were statistically significant determinants of persistent disease at the 6th month after surgery. The multivariate analysis revealed that higher IGF-I levels at diagnosis and the preoperative cavernous sinus invasion were each statistically significant prognostic factors of persistent disease.


CONCLUSIONS
A short administration of preoperative lanreotide 30 mg induced a statistically significant shrinkage of GH-secreting pituitary adenomas where this reduction was > 20% of the pretreatment value in 29% of the whole population. Among the factors considered was the fact that positive hormone response to preoperative lanreotide 30 mg was the sole predictive factor of this significant tumour volume reduction.
Lucas
Tomás
T
Department of Endocrinology, Clínica Puerta de Hierro, Madrid, Spain.
Astorga
Ricardo
R
Catalá
Miguel
M
D000236:Adenoma / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D003131:Combined Modality Therapy; D005260:Female; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000627:therapeutic use*; D010911:Pituitary Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D011446:Prospective Studies; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018972:Insulin-Like Growth Factor Binding Protein 3; D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone