Results of a two-year treatment with slow release lanreotide in acromegaly

In this open sequential study we evaluated the long-term effectiveness and tolerability of the i.m. administration of slow release lanreotide 30 mg (S RL) in 18 acromegalics (7 M/11 F, age 50.9+/-12.7 yr). Baseline mean GH and IGF-1 levels were 15.8+/-6.6 ng/ml and 702+/-74 ng/ml, respectively. Four hours, 1, 7, and 14 days after SRL, mean GH levels were 8.9+/-5.9 (p<0.005) , 11.4+/-6.9 (p<0.05), 9.1+/-4.5 (p<0.05), and 9.1+/-4.1 ng/ml (p<0.05), re spectively; and the IGF-1 values at 1, 7, and 14 days were 624+/-77 (p<0.05 ), 555+/-83 (p<0.001), and 467+/-58 ng/ml (p<0.0001), respectively. Four ho urs after SRL administration GH was <2.5 ng/ml in 11 patients and decreased 85 % of the basal value, without normalizing, in another case. In the foll owing 2 weeks, 7 and 2 patients maintained GH <2.5 ng/ml or <50 % of baseli ne; 3 and 2 of them attained IGF-1 values in the normal range or < 50% of b asal levels. A patient developed acute pancreatitis after the injection of the drug and therefore stopped the treatment. Another patient did not conti nue SRL, and she was turned on octreotide, s.c. administered (OCT), because only the latter treatment ameliorated significantly the headache. In 16/18 patients the treatment was continued until the 24th month. SRL was adminis tered every 14 days until the 24th month in 3 cases, whereas in 13 patients the dose schedule was increased every 10 days since the 7th month because they did not normalize serum CH and IGF-1 levels. In these 16 patients base line GH and IGF-1 levels were 10.0+/-2.5 ng/ml and 671+/-75 ng/ml, respecti vely. At the 1st, 3rd, and 6th month of treatment mean GH levels fell to 5. 4+/-1.4 (p<0.05), 5.3+/-1.8 (p<0.05), and 5.0+/-1.6 (p<0.05) ng/ml, respect ively; and IGF-1 declined to 511 +/- 87 (p<0.005), 565+/-85 (p<0.05), and 5 25+/-94 (p<0.01) ng/ml, respectively. Throughout the first semester GH was <2.5 ng/ml in 5 patients and decreased > 50% in another three. IGF-1 levels normalized in 3/5. Throughout the following 18 months of treatment, mean C H (3.4+/-1.0 ng/ml) and IGF-1 (413 +/-75 ng/ml) values decreased significan tly in comparison with both the baseline concentrations (CH p<0.01, IGF-1 p <0.001) and the levels measured during the 1st semester of treatment (CH p< 0.05, IGF-1 p<0.001). GH remained <2.5 ng/ml in 11 patients, and in 8/11 ca ses IGF-1 fell in the normal range. Serum CH and IGF-1 levels decreased by more than 50% of baseline levels in 2 other cases. At MRI, pituitary adenom a was no longer evident in one patient previously treated with OCT and sign ificantly decreased in another patient previously treated with surgery plus radiotherapy, as well as in a patient previously untreated. During treatme nt the percentage of patients complaining of headache and fatigue decreased significantly (chi(2), p<0.05 and p<0.0005, respectively). Overall, the he adache (p<0.005), arthralgia (p<0.05), and paresthesia (p<0.01)ameliorated significantly. Ultrasound scan showed gallbladder sludge or sand-like stone s in 5/11 patients. This study, which is one of the longest surveys on a re latively large series of acromegalics treated with SRL, confirms the long-t erm effectiveness of this drug for the treatment of patients with active ac romegaly. SRL decreases significantly CH and IGF-1 in most cases and induce s the shrinkage of the pituitary tumor in some patients previously either u ntreated or both treated for acromegaly. SRL improves significantly clinica l symptoms and it is well tolerated.