Efficacy and tolerability of the long-acting somatostatin analog lanreotide in acromegaly. A 12-month multicenter study of 58 acromegalic patients. French Multicenter Study Group on Lanreotide in Acromegaly.

Abstract

To determine the effects of the new somatostatin analogue, lanreotide, in its prolonged released form (PR), in patients with acromegaly. Prospective open multicenter non comparative study. Thirty-three university-affiliated medical centers. One hundred sixteen acromegalic patients with active disease, of whom 58 patients complied with the protocol and completed the 12-month period treatment. Lanreotide PR treatment was started at a dose of 30 mg intramuscularly every 14 days. If integrated mean plasma GH levels were not below 5 micrograms/L and/or IGF-I levels were not normalized after one month of treatment, injections were given every 10 days. The duration of the study was 12 months. After one month of treatment mean plasma GH and IGF-I levels had fallen from 10.7 +/- 11.1 micrograms/L (mean +/- SD; range, 2.6-74.8 micrograms/L; median, 7 micrograms/L) and 718 +/- 270 micrograms/L (range 338-1440 micrograms/L; median, 645 micrograms/L), respectively, to 7.8 +/- 10.1 micrograms/L and 575 +/- 252 micrograms/L, respectively. Thirty patients (22%) had plasma GH levels below 2.5 micrograms/L, and 8 patients (16%) had age-adjusted normal plasma IGF-I levels. At the sixth month of treatment mean plasma GH levels of 2.5 micrograms/L or less, and normal plasma IGF-I levels were observed in 33%, and 33% of patients, respectively. At the twelvth month of treatment, these percentages were 41%, and 41%, respectively. The interval between two injections was shortened (one injection every 10 days) in 8 of the 58 patients (13%) at the second month of treatment, and at the end of the study, 70% of patients required 3 injections per month. The most frequent adverse event elicited by enquiry was transient diarrhea (76% of patients), followed by abdominal pain (62%) and pain at the injection site (59%). Based on the analysis of a subgroup of 46 patients who had at least a measurement of fecal fat content after day 0 of the study, a non significant increase (from 4.2 +/- 3.4 to 5.1 +/- 4.3 g/24 h, p = 0.3) in mean steatorrhea was observed during treatment. Before treatment, steatorrhea was present in 9 (19%) patients. During the study, 15 additional patients (32%) developed persistent steatorrhea, and there was a transient increase in fecal fat content above 6 g/24 h in another 11 patients. After exclusion of the 7 patients (12%) with gallstones at enrollment, new gall-stones were diagnosed in 6 out of 50 patients (12%) during the study. Two or three monthly injections of lanreotide PR decreased GH concentration to less than 2.5 micrograms/L and normalized IGF-I levels in 41% of patients treated during 12 months. The good tolerability of this treatment, and the reduction in the frequency of injections, plus the sustained drug serum concentrations, confirm the usefulness of this new somatostatin analog formulation.