Primary Treatment of Acromegaly with Octreotide LAR: A Long-Term (Up to Nine Years) Prospective Study of Its Efficacy in the Control of Disease Activity and Tumor Shrinkage

Abstract

The efficacy on GH/IGF-I levels in unselected patients and the outstanding volumetric control indicate that treatment with OCLAR may be the first therapeutic approach to all acromegalic patients not amenable to surgical cure. Tumor shrinkage might also encourage the evaluation of primary OCLAR adoption in patients with initial visual field defects.

Somatostatin agonists for treatment of acromegaly

“…Several papers in recent years report the efficacy of primary pharmacotherapy in achieving biochemical disease control. Similar rates of patient control were achieved in the primary and adjuvant groups, with GH plasma levels ≤2.5 μg/L (64%) and/or normalization of IGF-1 (64%) Ayuk et al, 2002Ayuk et al, , 2004Bevan et al, 2002;Colao et al, 2001Colao et al, , 2006cCozzi et al, 2003Cozzi et al, , 2006. Even though de novo patients had higher pre-treatment GH or IGF-1 levels or both, than those already treated with surgery and/or radiotherapy, patients achieved the same ultimate level of biochemical control by the end of the study Cozzi et al, 2003).…”

“…Table 1 summarizes both primary and adjuvant pharmacotherapy results from studies lasting ≥6 months on >10 patients and shows 70% shrinkage with octreotide LAR, 26% with lanreotide SR 30 mg and 39% with lanreotide SR 60 mg. Recent studies of primary SRL pharmacotherapy suggest mean 79% tumor shrinkage with octreotide LAR Cozzi et al, 2003Cozzi et al, , 2006 and 50% with lanreotide 60 mg or 25% with lanreotide 30 mg Baldelli et al, 2000). Basal GH levels correlated positively with the degree of shrinkage which was >75% in 44% of patients in one study and >50% in 60% of patients in another .…”

“…If considering only GH levels <1 μg/L to be the cutoff for "normalizing" mortality, 33% of octreotide LAR Cozzi et al, 2003;Lancranjan and Atkinson, 1999;Lancranjan et al, 1996) and 25% of lanreotide SR Chanson et al, 2000a) treated patients achieved disease control, implying that ~50% of SRIF agonist treated GH-"controlled" patients may still be at higher risk for higher mortality rates. Prolonged treatment duration improves biochemical control as GH and IGF-1 plasma levels continue to decrease with time Colao et al, 2001;Cozzi et al, 2003Cozzi et al, ,2006Davies et al, 1998;Freda et al, 2005;Jallad et al, 2005;Ronchi et al, 2006). Primary pharmacotherapy is an optional treatment for selected patients (Ben-Shlomo and Melmed, 2003;Colao et al, 2006b).…”

Quality of life is impaired in association with the need for prolonged postoperative therapy by somatostatin analogs in patients with acromegaly

“…They also act on the liver to block the synthesis of IGF1 (4). In about 60% of patients treated with SSTA, biochemical control can be achieved (5,6). Other medical treatment options include GH receptor antagonists and dopamine agonists.…”

Antitumor effects of somatostatin

“…The efficacy of analogs on tumor growth is attributed to sst 2 and sst 5 whose expression predominates in growth hormone-secreting adenomas (Jaquet et al, 2000). Recent data argue in favour of a dissociation between antiproliferative and antisecretory effects of somatostatin analogs, their antitumor effect occuring independently of their antihormonal effect (Cozzi et al, 2006;Maiza et al, 2007). Somatostatin analog-resistant acromegalic patients may present tumor shrinkage without hormonal normalization, the former being related to a high expression of either sst5 or sst3.…”