神经内分泌肿瘤(NENs)是一组异质性癌症,在过去十年中每年的发病率显着增加。它们可分为高分化神经内分泌肿瘤(NETs)和低分化神经内分泌癌(NECs)。低分化的NEC是具有有限治疗选择的侵袭性癌症形式。转移性低分化NECs的一线治疗与小细胞肺癌相似,细胞毒性化疗(依托泊苷加铂)。进展的患者治疗选择有限,总体生存率低,呼吁其他新的代理人来对抗这种致命的疾病。因此,在这篇文章中,我们总结了一种新成分的作用,胸腺醌(TQ,C10H12O2),这是黑色种子的主要生物活性成分(Nigellasativa,毛竹科),在难治性转移性肺外NEC(EP-NEC)和1例混合性神经内分泌-非神经内分泌肿瘤(MiNEN)的病例系列中加上免疫治疗。
我们报告了TQ加双重免疫检查点抑制剂(nivolumab加ipilimumab)对4例分化低的胃肠道Ep-NEC和MiNEN患者的影响,这些患者在细胞毒性化疗中进展。
这是第一个报告TQ加双重免疫检查点抑制剂(nivolumab加ipilimumab)在难治性转移性EP-NEC患者中的临床活性的病例系列。4例患者在联合方案TQ加双重ICPIs的治疗中表现出持续反应的益处,并且超过了两年的无进展生存期。四名患者均未出现明显的毒性反应,所有这些都显示出生活质量的改善。
报道的临床过程表明,TQ加ICPIs联合治疗难治性EP-NEC和MiNEN是一种潜在的有希望的方案,值得进一步前瞻性研究。
Neuroendocrine neoplasms (NENs) are a heterogeneous group of cancers that had a significant increase in annual incidence in the last decade. They can be divided into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Poorly differentiated NECs are aggressive forms of cancers with limited therapeutic options. The first line treatment of metastatic poorly differentiated NECs is similar to small cell lung cancer, with cytotoxic chemotherapy (etoposide plus platinum). Patients who progress have limited therapeutic options and poor overall survival, calling for other novel agents to combat this deadly disease. Therefore, in this article, we summarized the effects of a novel component,
Thymoquinone (TQ, C10H12O2), which is the main bioactive component of the black seed (Nigella sativa, Ranunculaceae family), plus immunotherapy in
case series of patients with refractory metastatic extra-pulmonary NEC (EP-NEC) and one
case of mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN).
We report the effect of TQ plus dual immune checkpoint inhibitors (nivolumab plus ipilimumab) in four patients with poorly differentiated gastrointestinal Ep-NEC and MiNEN who progressed on cytotoxic chemotherapy.
This is the first
case series to report the clinical activity of TQ plus dual immune checkpoint inhibitors (nivolumab plus ipilimumab) in patients with refractory metastatic EP-NEC. The four patients showed benefits with the combined regimen TQ plus dual ICPIs with durable response and exceeded the two years of progression-free survival. None of the four patients experienced significant toxicity, and all of them showed improvement in quality of life.
The reported clinical courses suggest that combined TQ plus ICPIs is a potential promising regimen for refractory EP-NEC and MiNEN that deserves further prospective investigation.