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12 例黑色素瘤患者接受纳武利尤单抗治疗早期的血清 5-S-半胱氨酰多巴行为。

Serum 5-S-cysteinyldopa behavior in the early phase of nivolumab treatment of 12 melanoma patients.

机构信息

Department of Dermatology, Shinshu University School of Medicine, Matsumoto, Japan.

Department of Dermatology, Sapporo Medical University School of Medicine, Sapporo, Japan.

出版信息

J Dermatol. 2018 Nov;45(11):1340-1344. doi: 10.1111/1346-8138.14605. Epub 2018 Aug 25.

Abstract

Along with the expansion of therapeutic options for metastatic melanoma, the development of useful biomarkers is urgently required to predict and monitor treatment response. Serum 5-S-cysteinyldopa (5-S-CD) has been identified as a diagnostic marker of malignant melanoma, but its utility as a biomarker for emerging therapeutic agents remains unknown. We assessed serum 5-S-CD in 12 metastatic melanoma patients (median age, 76 years; six men and six women) who had been treated with nivolumab (Nivo) at Shinshu University Hospital between 2014 and 2016. Serum 5-S-CD and lactate dehydrogenase levels before and at 3-6 weeks of Nivo treatment were obtained and their changes were compared with clinical responses as defined by the Response Evaluation Criteria in Solid Tumors criteria (version 1.1). A decrease of 10 nmol/L or more of serum 5-S-CD was observed only in partial response patients (2/3 cases, 67%), while an increase of 10 nmol/L or more of serum 5-S-CD was witnessed only in progressive disease patients (4/8 cases, 50%). Serum 5-S-CD changes were within ±10 nmol/L in the remaining six patients (partial response, one; stable disease, one; progressive disease, four). The results of the four moderately affected progressive disease patients were suspected to have been influenced by small-sized metastatic lesions, a mixed response that included diminished and enlarged metastatic lesions, prior therapy to Nivo with BRAF inhibitors or radiation, or the development of brain metastasis. Serum 5-S-CD in the early phase of Nivo treatment may be helpful to predict therapeutic response in metastatic melanoma.

摘要

随着转移性黑色素瘤治疗选择的扩大,迫切需要开发有用的生物标志物来预测和监测治疗反应。血清 5-S-半胱氨酸(5-S-CD)已被确定为恶性黑色素瘤的诊断标志物,但作为新兴治疗药物的生物标志物的用途尚不清楚。我们评估了 2014 年至 2016 年间在信州大学医院接受纳武单抗(Nivo)治疗的 12 例转移性黑色素瘤患者(中位年龄 76 岁;男 6 例,女 6 例)的血清 5-S-CD。在 Nivo 治疗前和 3-6 周时获得血清 5-S-CD 和乳酸脱氢酶水平,并将其变化与实体瘤反应评估标准(版本 1.1)定义的临床反应进行比较。仅在部分缓解患者(2/3 例,67%)中观察到血清 5-S-CD 降低 10 nmol/L 或更多,而在进展性疾病患者(4/8 例,50%)中仅观察到血清 5-S-CD 增加 10 nmol/L 或更多。在其余 6 例患者(部分缓解 1 例,稳定疾病 1 例,进展性疾病 4 例)中,血清 5-S-CD 变化在±10 nmol/L 范围内。对 4 例中度进展性疾病患者的结果怀疑受到小转移病灶的影响,包括减少和增大的转移病灶的混合反应、Nivo 治疗前接受 BRAF 抑制剂或放疗、或脑转移的发生。Nivo 治疗早期的血清 5-S-CD 可能有助于预测转移性黑色素瘤的治疗反应。

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