High-dose and high-frequency lanreotide autogel in acromegaly: a randomized, multicenter study

CONTEXT: The increase in drug frequency or dose is recommended for acromegaly patients with partial response to long-acting somatostatin receptor ligands (SRLs). However, the efficacy and safety data with lanreotide autogel (LAN-ATG) at high-dose (HD) or high-frequency (HF) are still scanty and anecdotal. OBJECTIVE: To evaluate the biochemical efficacy and safety of HF- and HD LAN-ATG in patients with active acromegaly. DESIGN: 24-week prospective, multicentre, randomized, open-label trial. PATIENTS AND INTERVENTIONS: Thirty patients with active acromegaly, partial responder to SRL, were randomized to HF (120 mg/21 days; 15 patients) or HD (180 mg/28 days; 15 patients) LAN-ATG. OUTCOMES: Normalization of serum IGF-I and reduction in random GH values <1.0 µg/L, reduction in serum IGF-I and GH from baseline, differences in biochemical response between HF- and HD-LAN-ATG, safety/tolerability evaluations. RESULTS: Serum IGF-I decreased significantly (p=0.007) during 24-week treatment, with greater decrease in HD (p=0.03) as compared to HF group (p=0.08). Normalization in serum IGF-I values occurred in 27.6% of patients (p=0.016 vs. baseline), without significant difference between HF and HD groups (p=0.59). Decrease in serum IGF-I significantly correlated with serum lanreotide values (p=0.04) and normalization of IGF-I was predicted by baseline IGF-I values (p=0.02). Serum GH values did not change significantly (p=0.22). Overall, 19 patients (63.3%) experienced adverse events, all being mild to moderate and transient, without differences between the two therapeutic arms. CONCLUSION: HF- and HD- LAN-ATG regimens are effective in normalizing IGF-I values in about one-third of patients with active acromegaly inadequately controlled by long-term conventional SRL therapy.