Baldelli R, Colao A, Razzore P, Jaffrain-Rea M L, Marzullo P, Ciccarelli E, Ferretti E, Ferone D, Gaia D, Camanni F, Lombardi G, Tamburrano G
Department of Clinical Science, Endocrine Section, University of Rome La Sapienza, Italy.
J Clin Endocrinol Metab. 2000 Nov;85(11):4099-103. doi: 10.1210/jcem.85.11.6948.
Pharmacotherapy of acromegaly has been improved in recent years as new long-acting somatostatin analogs have became available; they have been suggested as an alternative treatment to pituitary surgery and radiotherapy. To avoid the inconvenience of multiple daily injections during long-term therapy, a slow release formulation of lanreotide (LAN), to be administered im at a dose of 30 mg every 7-14 days, has been introduced in the therapeutic management. The suppressive effects of a short-term LAN treatment on GH and insulin-like growth factor I (IGF-I) hypersecretion were shown to be similar to those obtained with sc octreotide. However, scant data have been reported concerning a long-term treatment with this drug. In the present study the efficacy and tolerability of a 24-month LAN treatment were evaluated in 118 active acromegalic patients; 71 had been previously operated on and treated with s.c. octreotide (operated patients), 24 previously operated on had been irradiated and treated with s.c. octreotide (irradiated patients), and the remaining 23 were newly diagnosed (de novo patients). The efficacy was considered on the basis of controlled GH (fasting, <7.5 mU/L; glucose-suppressed, <3.0 mU/L) and IGF-I (age-adjusted normal values) secretion. In the 118 patients as a whole, circulating GH and IGF-I levels were significantly decreased during the 24-month LAN treatment (P < 0.0005 at all time points vs. basal value). After 24 months of therapy, controlled GH and IGF-I levels were achieved in 64%, 37%, and 78% and in 51%, 37%, and 70% of operated, irradiated, and de novo patients, respectively. A reduction in tumor size was documented in 5 of 23 de novo patients (22%). Among the 84 operated/irradiated with evident tumor remnant, significant shrinkage was documented in 5 patients (5.9%). Treatment was well tolerated by the majority of patients. Only 2 patients (1.7%) withdrew from LAN treatment due to severe side effects. In conclusion, a 24-month treatment with slow release lanreotide (30 mg) is effective in reducing GH and IGF-I levels; furthermore, in de novo patients it induces disease control in 70% of patients and causes tumor shrinkage in 22% of them, with excellent compliance. These data suggest that LAN can be used in long-term treatment of acromegalic patients.
近年来，随着新型长效生长抑素类似物的出现，肢端肥大症的药物治疗有了改善；它们被建议作为垂体手术和放疗的替代治疗方法。为避免长期治疗期间每日多次注射带来的不便，已在治疗管理中引入了一种长效缓释兰瑞肽（LAN）制剂，以每7 - 14天30毫克的剂量进行肌肉注射。短期LAN治疗对生长激素（GH）和胰岛素样生长因子I（IGF - I）分泌过多的抑制作用显示与皮下注射奥曲肽相似。然而，关于这种药物长期治疗的报道数据很少。在本研究中，对118例活动性肢端肥大症患者进行了为期24个月的LAN治疗的疗效和耐受性评估；71例患者先前接受过手术并接受皮下注射奥曲肽治疗（手术患者），24例先前接受过手术的患者接受过放疗并接受皮下注射奥曲肽治疗（放疗患者），其余23例为新诊断患者（初发患者）。根据GH（空腹，<7.5 mU/L；葡萄糖抑制后，<3.0 mU/L）和IGF - I（年龄调整后的正常值）分泌的控制情况来评估疗效。在118例患者总体中，在24个月的LAN治疗期间循环GH和IGF - I水平显著降低（与基础值相比，所有时间点P < 0.0005）。治疗24个月后，手术患者、放疗患者和初发患者中分别有64%、37%和78%以及51%、37%和70%的患者实现了GH和IGF - I水平的控制。在23例初发患者中有5例（22%）记录到肿瘤大小缩小。在84例有明显肿瘤残留的手术/放疗患者中，有5例（5.9%）记录到肿瘤显著缩小。大多数患者对治疗耐受性良好。只有2例患者（1.7%）因严重副作用退出LAN治疗。总之，为期24个月的长效缓释兰瑞肽（30毫克）治疗在降低GH和IGF - I水平方面有效；此外，在初发患者中，它能使70%的患者病情得到控制，22%的患者肿瘤缩小，且依从性良好。这些数据表明LAN可用于肢端肥大症患者的长期治疗。
