Division of Oncology, Department of Internal Medicine I, Medical University Vienna, Vienna, Austria.
Neuroendocrine Tumor Unit, Comprehensive Cancer Center Vienna, Medical University Vienna, Vienna, Austria.
Oncologist. 2019 Feb;24(2):255-258. doi: 10.1634/theoncologist.2018-0191. Epub 2018 Aug 31.
Somatostatin analogs (SSAs) are standard for symptomatic patients with neuroendocrine tumors (NETs). However, most patients experience tachyphylaxis, and limited options exist for this so-called "refractory carcinoid syndrome." Recently, 5-HT antagonist ondansetron has been associated with reduction of bowel movement in a small series. The aim of this analysis was to assess effectiveness of ondansetron for symptomatic treatment of carcinoid syndrome.
We have analyzed patients given ondansetron as bridging therapy for refractory carcinoid syndrome. The dose was 2 × 8 mg for 5 days, followed by reduction to 1 × 8 mg in case of benefit.
A total of 14 patients with small bowel NETs metastatic to the liver were identified. All patients had been treated with SSAs for a median time of 18 months before aggravation of diarrhea. One patient had to be excluded because of an underlying infectious cause of diarrhea. The median number of daily bowel movements was 7 (range, 5-13) before initiation of therapy. At this time, seven patients had stable disease, whereas six patients showed radiological progression with symptomatic breakthrough. All 13 patients were scheduled for salvage therapy. Remarkably, in 85% (11/13) ondansetron resulted in a clinically relevant decrease of bowel movements to a median of 3 (1-4). The median time of ondansetron intake was 29 days (7 days to 29 months). In four patients, diarrhea recurred after initial improvement at an interval of 22-43 days, whereas the remaining seven had an ongoing benefit, including two long-term responders who refused further therapy because of pronounced decrease of symptoms (ondansetron for 14+ and 29+ months).
Ondansetron offers symptomatic relief in the majority of patients. Although there was no influence on 5-HIAA levels, evidence from two patients suggests prolonged benefit.
Somatostatin analogs are standard treatment in patients with carcinoid syndrome and have an overall response rate of up to 50%. This symptomatic benefit, however, is lost in many patients because of the development of tachyphylaxis or tumor progression. Patients with this "refractory carcinoid syndrome" pose a therapeutic challenge and are sometimes faced with a detrimental effect on quality of life. In this article, the authors suggest the 5-HT receptor antagonist ondansetron as potential symptomatic therapy for patients with refractory diarrhea due to carcinoid syndrome. Although the number of patients in this retrospective series is limited, treatment was easily applicable, feasible, and safe and resulted in an ongoing symptomatic benefit in 85% of patients, including two long-term responders.
生长抑素类似物（SSAs）是神经内分泌肿瘤（NETs）有症状患者的标准治疗方法。然而，大多数患者会出现快速耐受，并且对于这种所谓的“难治性类癌综合征”，选择有限。最近，5-HT 拮抗剂昂丹司琼与减少小系列的肠蠕动有关。本分析的目的是评估昂丹司琼对类癌综合征症状治疗的有效性。
我们分析了接受昂丹司琼作为难治性类癌综合征桥接治疗的患者。剂量为 2×8mg，连用 5 天，如果有效，则减少至 1×8mg。
共确定了 14 例小肠 NET 转移至肝脏的患者。所有患者在腹泻加重前均接受 SSA 治疗中位时间为 18 个月。由于腹泻的潜在感染原因，有 1 例患者被排除在外。开始治疗前，每日排便次数中位数为 7 次（范围为 5-13 次）。此时，7 例患者疾病稳定，而 6 例患者出现放射学进展并出现症状突破。所有 13 例患者均计划进行挽救治疗。值得注意的是，昂丹司琼在 85%（11/13）的患者中，将排便次数明显减少至中位数 3 次（1-4 次），具有临床相关性。昂丹司琼的中位摄入时间为 29 天（7 天至 29 个月）。在 4 例患者中，初始改善后腹泻复发，间隔 22-43 天，而其余 7 例患者持续受益，包括 2 例长期反应者，因症状明显减轻而拒绝进一步治疗（昂丹司琼治疗 14+和 29+个月）。
昂丹司琼为大多数患者提供了症状缓解。尽管对 5-HIAA 水平没有影响，但来自两名患者的证据表明存在长期益处。
生长抑素类似物是类癌综合征患者的标准治疗方法，总体反应率高达 50%。然而，由于快速耐受或肿瘤进展，许多患者会失去这种症状益处。患有这种“难治性类癌综合征”的患者具有治疗挑战性，有时会对生活质量产生不利影响。在本文中，作者建议使用 5-HT 受体拮抗剂昂丹司琼作为难治性腹泻类癌综合征患者的潜在症状治疗方法。尽管这项回顾性研究的患者数量有限，但治疗易于应用、可行且安全，85%的患者持续受益，包括 2 例长期反应者。
