Endocrine Abstracts (2009) 20 OC4.1

High-dose octreotide LAR in patients with acromegaly inadequately controlled by conventional somatostatin analogue therapy: a randomized, controlled trial

Andrea Giustina1, Stefania Bonadonna1, Giovanna Bugari1, Annamaria Colao2, Renato Cozzi3, Salvatore Cannavò4, Laura De Marinis5, Ettore degli Uberti6, Fausto Bogazzi7, Gherardo Mazziotti1, Francesco Minuto8, Marcella Montini9 & Ezio Ghigo10

1University of Brescia, Brescia, Italy; 2University Federico II, Naples, Italy; 3Niguarda Hospital, Milan, Italy; 4University of Messina, Messina, Italy; 5Catholic University, Rome, Italy; 6University of Ferrara, Ferrara, Italy; 7University of Pisa, Pisa, Italy; 8University of Genova, Genova, Italy; 9Bergamo Hospital, Bergamo, Italy; 10University of Turin, Turin, Italy.

Objective: In acromegaly, 25–50% of patients remain uncontrolled with conventional somatostatin analogue (SA) therapy. Evidence suggests that response may be improved by increasing the dose or frequency of administration of SAs. This study evaluated the efficacy and safety of octreotide LAR administered at a high dose or high frequency in patients with acromegaly.

Methods: This was a 24-week prospective, multicenter, randomized, open-label trial in patients with active acromegaly despite ≥6 months’ conventional maximal-dose SA therapy. Patients had baseline GH>2.0 μg/l, elevated IGF-I for age/sex-matched controls and had a ≥50% reduction in GH during previous SA treatment. Patients were randomized to receive high-dose (60 mg/28 d; n=11) or high-frequency (30 mg/21 d; n=15) octreotide LAR for 24 weeks. The primary endpoint was change from baseline in GH and IGF-I at week 24. Secondary endpoints included IGF-I normalization, tumor shrinkage, safety and tolerability.

Results: In the high-dose group only, a significant change from baseline was seen for mean GH (−28%; P=0.046) and IGF-I (−27%; P=0.023). In the high-frequency group, changes from baseline in mean GH (+6.4%) and IGF-I (−4.7%) were not statistically significant. Significantly more patients in the high-dose group achieved a reduction in IGF-I at week 24 than those in the high-frequency group (91 vs 53%; P<0.05). IGF-I normalization or GH<2 μg/l occurred with only the high-dose regimen (IGF-I 36 vs 0%, P=0.022; GH 27 vs 0%, P=0.06). The proportion of patients experiencing tumor shrinkage was similar in the high-frequency and high-dose groups (14 vs 11%). Both regimens were well tolerated.

Conclusion: High-dose octreotide LAR (60 mg/28 d) is effective and well tolerated in patients with active acromegaly inadequately controlled with conventional SA therapy. These results suggest that in selected patients uncontrolled on conventional doses of SAs, high-dose octreotide LAR should be tried before switching to other treatment modalities.