Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.
Department of Advanced Biomedical Sciences, Radiology, Section of Diagnostic Imaging, University "Federico II", Naples, Italy.
Endocrine. 2018 Oct;62(1):46-56. doi: 10.1007/s12020-018-1583-7. Epub 2018 Mar 23.
Medullary thyroid cancer (MTC) is a neuroendocrine tumour of the thyroid C cells. Pasireotide, a multi-receptor targeted somatostatin analogue, and everolimus, an inhibitor of mTOR, showed antitumour properties in neuroendocrine tumours. Aim of this study was to evaluate pasireotide alone and in combination with everolimus in patients with MTC.
Patients with progressive metastatic or persistent postoperative MTC received pasireotide LAR 60 mg/m for at least 6 months. Patients exhibiting progressive disease received everolimus 10 mg/d as combination therapy. Primary endpoint was progression free survival (PFS). Secondary endpoints included, overall survival, objective response rates, change in circulating markers, safety. Study registration no. NCT01625520.
Nineteen consecutive patients were enrolled. Median follow-up was 31 months. Median PFS with pasireotide was 36 months (95% CI: 19.5-52.5). Nine patients (47%) had tumour progression: seven of them started everolimus in combination with pasireotide, achieving a median PFS of 9.0 months (95% CI: 0-21.83). Five of them (71%) had further tumour progression, one objective response (14.3%), one stopped treatment because of pulmonary embolism. Pasireotide alone and with everolimus was safe and required withdrawal only in one case. Diarrhoea and hyperglycaemia were the most frequent adverse events with pasireotide (grade 3 in 5.3% each). Hyperglycaemia was the most frequent grade 3 toxicity with the combination therapy (28.6%).
Pasireotide therapy shows antiproliferative effects in persistent postoperative MTC suggesting further investigation on larger series of patients. In progressive MTC lesions, the combination pasireotide plus everolimus may be of benefit. Both schemes were safe and well tolerated.
甲状腺髓样癌（MTC）是甲状腺 C 细胞的神经内分泌肿瘤。帕瑞肽是一种多受体靶向生长抑素类似物，依维莫司是 mTOR 抑制剂，在神经内分泌肿瘤中显示出抗肿瘤特性。本研究旨在评估帕瑞肽单药及联合依维莫司在 MTC 患者中的疗效。
进展性转移性或持续性手术后 MTC 患者接受帕瑞肽 LAR 60mg/m 至少 6 个月。疾病进展的患者接受依维莫司 10mg/d 联合治疗。主要终点是无进展生存期（PFS）。次要终点包括总生存期、客观缓解率、循环标志物变化、安全性。研究注册号：NCT01625520。
连续入组 19 例患者。中位随访时间为 31 个月。帕瑞肽的中位 PFS 为 36 个月（95%CI：19.5-52.5）。9 例患者（47%）发生肿瘤进展：其中 7 例开始帕瑞肽联合依维莫司治疗，中位 PFS 为 9.0 个月（95%CI：0-21.83）。其中 5 例（71%）肿瘤进一步进展，1 例客观缓解（14.3%），1 例因肺栓塞停止治疗。帕瑞肽单药及联合依维莫司治疗安全，仅 1 例因不良反应停药。腹泻和高血糖是帕瑞肽最常见的不良反应（各 5.3%为 3 级）。联合治疗最常见的 3 级毒性是高血糖（28.6%）。
帕瑞肽治疗对持续性手术后 MTC 具有抗增殖作用，提示对更大系列的患者进行进一步研究。在进展性 MTC 病变中，帕瑞肽联合依维莫司可能有益。两种方案均安全且耐受良好。
