Hematology-Oncology Unit, Fourth Department of Internal Medicine, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Department of Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
J Neuroendocrinol. 2022 Jul;34(7):e13174. doi: 10.1111/jne.13174. Epub 2022 Jul 6.
This review reports on the currently available medical treatment options for the control of symptoms due to carcinoid syndrome in patients with neuroendocrine tumors. The efficacy and adverse events (AEs) of approved drugs such as somatostatin analogues (SSA), telotristat ethyl (TE) and interferon-alpha, are reviewed. Somatostatin analogues remain the standard treatment of carcinoid syndrome based on the high expression of somatostatin receptors and the resulting inhibition of secretion of bioactive compounds; their use is associated with relatively mild AEs, involving mainly the gastrointestinal system, and being usually transient. Although dose escalation of SSA remains an unapproved option, it is clinically implemented to alleviate symptoms in refractory carcinoid syndrome and supported by the most recent guidelines. The side effects associated with the increased dose are in general mild and consistent with standard dose of SSA. Telotristat ethyl, an oral inhibitor of tryptophan hydroxylase, the rate-limiting enzyme in serotonin biosynthesis, represents a rather novel innovative treatment option in patients with carcinoid syndrome suffering from diarrhea and complements the standard therapy of SSA. Given the low toxicity profile, TE may be considered an early add-on treatment to SSA in patients with uncontrolled carcinoid syndrome. However, further prolonged follow-up of patients treated with TE may be needed to exclude potential AEs, such as liver toxicity or depressed mood, in patients with long-term treatment. Interferon alpha is a cytokine with direct inhibitory effect on hormone secretion and tumor cell proliferation and an approved therapy in carcinoid syndrome but is associated with significant AEs in the majority of the patients requiring frequently dose reduction. The finding of a more favorable tolerability of pegylated interferon needs to be confirmed in a prospective study.
这篇综述报告了目前可用于控制神经内分泌肿瘤患者类癌综合征症状的医疗治疗选择。审查了批准药物（如生长抑素类似物[SSA]、替罗瑞特乙酯[TE]和干扰素-α）的疗效和不良反应（AE）。基于生长抑素受体的高表达和由此抑制生物活性化合物的分泌，生长抑素类似物仍然是类癌综合征的标准治疗方法；其使用与相对较轻的 AE 相关，主要涉及胃肠道系统，且通常是短暂的。尽管 SSA 的剂量升级仍然是未经批准的选择，但它在临床上被用于缓解难治性类癌综合征的症状，并得到最新指南的支持。与增加剂量相关的副作用通常是轻微的，与 SSA 的标准剂量一致。替罗瑞特乙酯是色氨酸羟化酶的口服抑制剂，是 5-羟色胺生物合成的限速酶，是类癌综合征腹泻患者的一种相当新颖的创新治疗选择，补充了 SSA 的标准治疗。鉴于其低毒性特征，TE 可被认为是 SSA 治疗失败的患者的早期附加治疗。然而，可能需要对接受 TE 治疗的患者进行进一步的长期随访，以排除长期治疗患者中潜在的 AE，如肝毒性或情绪低落。干扰素-α是一种细胞因子，对激素分泌和肿瘤细胞增殖具有直接抑制作用，是类癌综合征的一种批准疗法，但在大多数患者中会引起明显的不良反应，需要经常减少剂量。聚乙二醇化干扰素具有更好耐受性的发现需要在前瞻性研究中得到证实。
