Variable growth hormone profiles following withdrawal of long-term 30 mg slow-release lanreotide treatment in acromegalic patients: Clinical implications

Abstract

Objective: Intramuscular injections of 30 mg slow-release (SR) lanreotide (every 10 to 14 days) are an effective treatment in acromegalic patients. Because of an ongoing need to assess the efficacy and the tolerance of a new formulation of a depot preparation of lanreotide, we have evaluated prospectively GH profiles following withdrawal of 30 mg slow-release lanreotide in a cohort of acromegalic patients. Patients: Fifty-one acromegalic patients, controlled during long-term 30 mg SR lanreotide treatment (GH: 1.44 ± 0.64 μg/l, IGF-I: 316 ± 145 ng/ml) (mean ± S.D.), were studied following the withdrawal of the drug. Measurements: Mean GH (half-hour samples, 0800-1200 h), IGF-I and lanreotide levels were evaluated 14, 28, and 42 days following the last 30 mg SR lanreotide injection. Results: Mean GH levels remained below 2.5 μg/l in 32 patients (group 1) twenty-eight days following SR lanreotide withdrawal. In these patients, mean GH and IGF-I levels had increased from 1.2 ± 0.6 to 1.7 ± 0.5 μg/l (P < 0001), and from 283 ± 138 to 359 ± 168 ng/ml (P < 0.001) respectively. In the 19 other patients (group 2), mean GH concentrations had risen above 2.5 μg/l at 28 days following SR lanreotide withdrawal. Mean GH and IGF-I levels had increased from 1.9 ± 0.4 to 5.1 ± 2.8 μg/l (P < 0.001), and from 371 ± 143 to 568 ± 206 ng/ml (P < 0.001) respectively. Patients of groups 1 and 2 were comparable with regard to age, sex, tumoral status, mean GH levels before somatostatin analogue treatment, and previous treatments such as radiotherapy and duration of somatostatin analogue therapy, but 75% of group 1 patients underwent surgery compared with 37% of group 2 patients (P < 0.01). Twenty-eight days following SR lanreotide withdrawal, mean lanreotide levels in group 1 and group 2 had decreased from 1.6 ± 0.7 to 0.6 ± 0.3 ng/ml (P < 0.001), and from 2.7 ± 2.0 to 0.7 ± 0.7 ng/ml (P < 0.001) respectively. A negative correlation was observed between the lanreotide levels and GH and IGF-I concentrations in the two groups of patients, but the inhibition of GH/IGF-I concentrations by lanreotide levels was higher in group 1 patients than in those of group 2. Six patients of group 1 were treated with 30 mg SR lanreotide injected at monthly intervals. During monthly follow-up, mean GH levels increased above 2.5 μg/l in 2 patients. After 12 months follow-up, mean GH and IGF-I levels from 4 other patients were similar to those obtained with previous therapeutic sequence (i.e. intramuscular injections every 14 days). Conclusion: The degree of responsiveness to lanreotide and the duration of somatotroph suppression following lanreotide withdrawal are variable in acromegalic patients controlled during long-term 30 mg SR lanreotide treatment. In patients displaying high sensitivity to lanreotide, the interval between i.m. 30 mg SR lanreotide injections can be increased to one month, thus reducing the cost of the therapy, without altering its efficacy upon GH/IGF-I control.