Rapid and sustained reduction of serum growth hormone and insulin-like growth factor-1 in patients with acromegaly receiving lanreotide Autogel therapy: a randomized, placebo-controlled, multicenter study with a 52 week open extension.
The study was designed to evaluate the long-term efficacy and safety of the 28-day prolonged-release Autogel formulation of the somatostatin analogue lanreotide (Lan-Autogel) in unselected patients with acromegaly. The study comprised four phases: washout; a double-blind comparison with placebo, at a single randomized dose (60, 90 or 120 mg) of Lan-Autogel; a single-blind, fixed-dose phase for four injections (placebo group was re-allocated to active treatment); and eight injections with doses tailored according to biochemical response. Serum samples were assessed for growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels, at weeks 4, 13, 14, 15, 16, 32 and 52. 108 patients were enrolled and 99 completed 52 weeks' treatment. Four weeks after the first injection, serum GH levels decreased by >50% from baseline in 63% of patients receiving Lan-Autogel compared with 0% receiving placebo (P < 0.001). After four injections, 72% of patients had a >50% reduction in GH levels; 49% patients achieved GH levels < or = 2.5 ng/ml; 54% had normalized IGF-1; and 38% achieved the combined criterion of GH level < or = 2.5 ng/ml and normalized IGF-1. The corresponding proportions by week 52 were 82, 54, 59 and 43%, respectively. In patients not requiring dose escalation to 120 mg, 85% achieved biochemical control (combined criterion). Treatment was well tolerated by all patients. In conclusion, Lan-Autogel was effective in controlling GH and IGF-1 hypersecretion in patients with acromegaly and showed a rapid onset of action.
Melmed
Shlomo
S
Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Shlomo.melmed@cshs.org
Cook
David
D
Schopohl
Jochen
J
Goth
Miklos I
MI
Lam
Karen S L
KS
Marek
Josef
J
D000172:Acromegaly / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D000328:Adult; D000367:Age Factors; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D019382:Human Growth Hormone / Q000097:blood / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000008:administration & dosage* / Q000009:adverse effects; D012737:Sex Factors; D013004:Somatostatin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
D000970:Antineoplastic Agents; D010456:Peptides, Cyclic; C060347:lanreotide; D019382:Human Growth Hormone; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I