Marzullo P, Ferone D, Di Somma C, Pivonello R, Filippella M, Lombardi G, Colao A
Department of Molecular and Clinical Endocrinology and Oncology, Federico II University, Naples, Italy.
Pituitary. 1999;1(2):115-20. doi: 10.1023/a:1009932521242.
The aim of this study was to evaluate the efficacy of a 6-month treatment with lanreotide (LAN) (60-90 mg/month) alone and combined with cabergoline (CAB) (1.5-3 mg/week) in 10 acromegalic patients previously demonstrated to be poor responders to octreotide (OCT) (0.6 mg/day) alone and combined with quinagolide (CV) (0.6 mg/day). All patients had previously undergone unsuccessful surgery and none of them received radiotherapy. Immunohistochemistry showed intense positive GH staining in all adenomas, positive PRL staining in 5 adenomas and faint ACTH or FSH/LH positive staining in other 2 adenomas. Moderately elevated serum PRL levels (35 and 47 ng/ml) were recorded in two patients. Fasting plasma IGF-I and serum GH levels were assayed at baseline and 30, 60, 90 and 120 days after each treatment. Gallbladder ultrasonography and sellar MRI were performed before and after 6 months of OCT and LAN treatments. After OCT treatment circulating GH and IGF-I levels remained elevated in all patients, while after 3 months of combined OCT + CV treatment, serum GH levels were suppressed (below 2.5 ng/ml) in only 1 patient. Significant increase of the percent GH (83.9 +/- 4.3 vs. 70.3 +/- 5.6%, p < 0.01) and IGF-I suppression (54 +/- 4.4 vs. 45.3 +/- 5.7, p < 0.01) and decrease of the nadir of GH (8.5 +/- 1.2 vs. 14.6 +/- 1.9 ng/ml, p < 0.01) and IGF-I (400.9 +/- 32.8 vs. 462.1 +/- 45.1 ng/ml) were obtained with the combined treatment when compared to OCT treatment alone. After a 15-30 days wash-out, circulating GH and IGF-I levels significantly increased up to pretreatment level in all patients. After 6 months of treatment with LAN, suppression of serum GH was achieved in 1 patient, but no difference in GH (66.3 +/- 6.3%) and IGF-I (43.9 +/- 4.6%) suppression was recorded in comparison to OCT treatment. After 3 months of treatment with LAN combined with CAB, suppression of serum GH and normalization of plasma IGF-I levels was achieved in 4 and 5 patients, respectively. Percent suppression of GH (88.1 +/- 2.1%) and IGF-I (57.5 +/- 2.8%) was significantly greater with the combined treatment than with LAN treatment alone. In the 7 patients with evident residual mass no change was documented by magnetic resonance imaging (MRI). None of the patients withdrew LAN + CAB treatment for poor tolerance, one patient had mild hypotension. Sludge was shown after 6 months of LAN treatment in one patient without notable change after 3 months of LAN + CAB treatment. In conclusion, the treatment with dopaminergic drugs such as CV and CAB, significantly increased the efficacy of somatostatin analogs, and can be used in combined therapy in poorly responsive patients.
本研究的目的是评估10例肢端肥大症患者单独使用兰瑞肽（LAN）（60 - 90mg/月）以及联合卡麦角林（CAB）（1.5 - 3mg/周）进行6个月治疗的疗效。这些患者之前已被证明对单独使用奥曲肽（OCT）（0.6mg/天）以及联合喹高利特（CV）（0.6mg/天）反应不佳。所有患者此前手术均未成功，且均未接受放疗。免疫组织化学显示所有腺瘤中生长激素（GH）染色呈强阳性，5例腺瘤中催乳素（PRL）染色呈阳性，另外2例腺瘤中促肾上腺皮质激素（ACTH）或促卵泡激素/促黄体生成素（FSH/LH）染色呈弱阳性。两名患者血清PRL水平中度升高（分别为35和47ng/ml）。在每次治疗前的基线以及治疗后30、60、90和120天检测空腹血浆胰岛素样生长因子 - I（IGF - I）和血清GH水平。在奥曲肽和兰瑞肽治疗6个月前后进行胆囊超声检查和蝶鞍磁共振成像（MRI）。奥曲肽治疗后所有患者循环GH和IGF - I水平仍升高，而奥曲肽 + 喹高利特联合治疗3个月后，仅1例患者血清GH水平被抑制（低于2.5ng/ml）。与单独使用奥曲肽治疗相比，联合治疗使GH抑制百分比（83.9±4.3%对70.3±5.6%，p < 0.01）和IGF - I抑制百分比（54±4.4对45.3±5.7，p < 0.01）显著增加，同时使GH最低点（8.5±1.2对14.6±1.9ng/ml，p < 0.01）和IGF - I（400.9±32.8对462.1±45.1ng/ml）降低。在15 - 30天的洗脱期后，所有患者循环GH和IGF - I水平显著升高至治疗前水平。兰瑞肽治疗6个月后，1例患者血清GH得到抑制，但与奥曲肽治疗相比，GH（66.3±6.3%）和IGF - I（43.9±4.6%）抑制率无差异。兰瑞肽联合卡麦角林治疗3个月后，分别有4例和5例患者血清GH被抑制且血浆IGF - I水平恢复正常。联合治疗的GH抑制百分比（88.1±2.1%）和IGF - I抑制百分比（57.5±2.8%）显著高于单独使用兰瑞肽治疗。在7例有明显残留肿块的患者中，磁共振成像（MRI）未显示有变化。没有患者因耐受性差而停用兰瑞肽 + 卡麦角林治疗，1例患者出现轻度低血压。1例患者在兰瑞肽治疗6个月后出现胆囊泥沙样改变，在兰瑞肽 + 卡麦角林治疗3个月后无明显变化。总之，使用多巴胺能药物如喹高利特和卡麦角林治疗可显著提高生长抑素类似物的疗效，可用于反应不佳患者的联合治疗。
