Pasireotide and Pegvisomant Combination Treatment in Acromegaly Resistant to Second-Line Therapies: A Longitudinal Study
Pasireotide and Pegvisomant Combination Treatment in Acromegaly Resistant to Second-Line Therapies: A Longitudinal Study
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DOI：
10.1210/jc.2019-00825
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发表时间：
2019-11-01
影响因子：
5.8
通讯作者：
Bianchi, Antonio
中科院分区：
文献类型：
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作者：
Chiloiro, Sabrina;Bima, Chiara;Bianchi, Antonio
内容：对一线和二线治疗耐药的肢端肥大症的治疗极具挑战性。设计：我们已经描述了6例成功接受帕瑞肽和培维索芒联合治疗的患者，并将其与对常规生长抑素类似物（SSA）耐药的对照组患者进行了比较，后者的疾病通过其他治疗得到控制，如帕瑞肽（单药治疗）或培维索曼（单药治疗或与常规SSA联合治疗）。结果：在这6例患者中，在所有其他治疗失败后，帕瑞肽和培维索曼联合治疗控制了肢端肥大症。与对照组的49例患者相比，这6例患者有巨大和侵袭性垂体腺瘤（海绵窦和其他结构）。虽然没有统计学显著性，但与对照组相比，接受帕瑞肽和培维索芒联合治疗的患者在肢端肥大症诊断时检测到更高的生长激素水平、更高的Ki-67表达、更高的生长抑素受体（SSTR）亚型5表达和更低的SSTR亚型2表达。我们的数据加强了根据临床、生化、分子生物学、免疫学和免疫学指标对肢端肥大症患者进行个性化治疗的重要性，和形态学疾病标志物，并表明帕瑞肽和pegvisomant的联合治疗可诱导SSTR 2表达低的肿瘤的疾病控制，对常规SSA（单独或与pegvisomant联合使用）和新一代SSA（单独使用帕瑞肽）具有耐药性。
Context: The treatment of acromegaly resistant to first- and second-line therapies can be extremely challenging.Design: We have described six patients who were successfully treated with a combination therapy of pasireotide and pegvisomant and compared them with a control group of patients resistant to conventional somatostatin analogs (SSAs), whose disease was controlled with other treatment, such as pasireotide (as monotherapy) or pegvisomant (as monotherapy or combined with conventional SSAs).Results: In these six patients, acromegaly was controlled with combined pasireotide and pegvisomant treatment after failure of all other treatments. Compared with the 49 patients in the control group, these six patients had giant and invasive pituitary adenomas (at both the cavernous sinus and other structures). Although not statistically significant, higher growth hormone levels, more elevated Ki-67 expression, greater somatostatin receptor (SSTR) subtype 5 expression, and lower SSTR subtype 2 expression at the diagnosis of acromegaly were detected in patients receiving combination treatment with pasireotide and pegvisomant compared with the control group.Conclusion: Our data have reinforced the importance of personalized treatment of patients with acromegaly according to the clinical, biochemical, molecular, and morphological disease markers and suggest that combined treatment with pasireotide and pegvisomant can induce disease control in tumors with low SSTR2 expression, resistant to conventional SSAs (alone or combined with pegvisomant) and to new-generation SSAs alone (pasireotide).