Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan.
Endocr J. 2013;60(5):651-63. doi: 10.1507/endocrj.ej12-0417. Epub 2013 Jan 19.
The somatostatin analog lanreotide Autogel has proven to be efficacious for treating acromegaly in international studies and in clinical practices around the world. However, its efficacy in Japanese patients has not been extensively evaluated. We examined the dose-response relationship and long-term efficacy and safety in Japanese patients with acromegaly or pituitary gigantism. In an open-label, parallel-group, dose-response study, 32 patients (29 with acromegaly, 3 with pituitary gigantism) received 5 injections of 60, 90, or 120 mg of lanreotide Autogel over 24 weeks. Four weeks after the first injection, 41% of patients achieved serum GH level of <2.5 ng/mL and insulin-like growth factor-I (IGF-I) level was normalized in 31%. Values at Week 24 were 53% for GH and 44% for IGF-I. Dose-dependent decreases in serum GH and IGF-I levels were observed with dose-related changes in pharmacokinetic parameters. In an open-label, long-term study, 32 patients (30 with acromegaly, 2 with pituitary gigantism) received lanreotide Autogel once every 4 weeks for a total of 13 injections. Dosing was initiated with 90 mg and adjusted according to clinical responses at Weeks 16 and/or 32. At Week 52, 47% of patients had serum GH levels of <2.5 ng/mL and 53% had normalized IGF-I level. In both studies, acromegaly symptoms improved and treatment was generally well tolerated although gastrointestinal symptoms and injection site induration were reported. In conclusion, lanreotide Autogel provided early and sustained control of elevated GH and IGF-I levels, improved acromegaly symptoms, and was well tolerated in Japanese patients with acromegaly or pituitary gigantism.
奥曲肽微球长效注射剂已被证明在国际研究和世界各地的临床实践中对肢端肥大症的治疗有效。然而,其在日本患者中的疗效尚未得到广泛评估。我们研究了奥曲肽微球长效注射剂在日本肢端肥大症或垂体巨人症患者中的剂量反应关系、长期疗效和安全性。在一项开放标签、平行分组、剂量反应研究中,32 例(29 例肢端肥大症,3 例垂体巨人症)患者接受了 24 周内 5 次 60、90 或 120 mg 奥曲肽微球长效注射剂的治疗。首次注射后 4 周,41%的患者血清 GH 水平<2.5ng/ml,31%的患者 IGF-I 水平正常。第 24 周时,GH 水平为 53%,IGF-I 水平为 44%。随着药代动力学参数的剂量相关性变化,观察到血清 GH 和 IGF-I 水平的剂量依赖性降低。在一项开放标签、长期研究中,32 例(30 例肢端肥大症,2 例垂体巨人症)患者每 4 周接受一次奥曲肽微球长效注射剂治疗,共接受 13 次注射。起始剂量为 90mg,并根据第 16 周和/或第 32 周的临床反应进行调整。第 52 周时,47%的患者血清 GH 水平<2.5ng/ml,53%的患者 IGF-I 水平正常。在这两项研究中,肢端肥大症症状均得到改善,且治疗总体上耐受性良好,尽管报告了胃肠道症状和注射部位硬结。总之,奥曲肽微球长效注射剂为日本肢端肥大症或垂体巨人症患者提供了早期和持续的 GH 和 IGF-I 水平控制,改善了肢端肥大症症状,且耐受性良好。