RRx-001 Priming of PD-1 Inhibition in the Treatment of Small Cell Carcinoma of the Vagina: A Rare Gynecological Tumor.
RRx-001 Priming of PD-1 Inhibition in the Treatment of Small Cell Carcinoma of the Vagina: A Rare Gynecological Tumor.
复制标题
RRx-001 启动 PD-1 抑制治疗阴道小细胞癌：一种罕见的妇科肿瘤。
DOI：
10.1159/000464101
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发表时间：
2017
影响因子：
0.8
通讯作者：
Brown,James
中科院分区：
文献类型：
--
作者：
Brzezniak,Christina;Oronsky,Bryan;Trepel,Jane;SummersJr,ThomasA;Cabrales,Pedro;Lee,Min-Jung;Day,Regina;Jha,Saheli;Caroen,Scott;Zeman,Karen;Ferry,Lindsey;Harmer,Cindy;Oronsky,Neil;Lybeck,Michelle;Lybeck,HarryE;Brown,James
阴道小细胞癌是罕见的，事实上，英语杂志上报道的总数不到30例。由于这种极低的发病率，没有建立具体的治疗指南，临床上已知的大多数来自少数单一病例报告。然而，由于适合其高度侵袭性的组织学特征，这让人想起小细胞肺癌（SCLC），一线治疗是仿照SCLC。本文报告了一例51岁的非裔美国患者，患有转移性活检证实的阴道小细胞癌，通过多种治疗进展：一线顺铂和依托泊苷（使其对铂耐药）和放疗，随后在一项名为QUADRUPLE THREAT的临床试验中使用肿瘤巨噬细胞刺激剂RRx-001，根据方案，在顺铂和依托泊苷强制再激发之前。RRx-001和顺铂/依托泊苷治疗的RECIST v. 1.1肿瘤进展伴有几个肿大淋巴结和肝转移灶的中央坏死，这可能是假进展的证据，解释了她持续的生存期长于预期，因为坏死组织可能引发了PD-1抑制剂的活性。假设对RRx-001缺乏反应与治疗前和治疗后活检中观察到的稀疏肿瘤巨噬细胞浸润相关，因为RRx-001的作用机制与刺激肿瘤相关巨噬细胞有关。
Small cell carcinoma of the vagina is rare, so rare in fact that the total number reported in English-language journals is less than 30. Due to this extremely low incidence, no specific treatment guidelines have been established, and most of what is clinically known is derived from a handful of single case reports. However, as befitting its highly aggressive histologic features, which are reminiscent of small cell lung cancer (SCLC), first-line treatment is modeled after SCLC. Herein is reported the case of a 51-year-old African-American patient with metastatic biopsy-proven small cell carcinoma of the vagina that progressed through multiple therapies: first-line cisplatin and etoposide (making it platinum-resistant) and radiotherapy, followed by the tumor macrophage-stimulating agent RRx-001 in a clinical trial called QUADRUPLE THREAT, which per protocol preceded a mandated rechallenge with cisplatin and etoposide. RECIST v. 1.1 tumor progression on both RRx-001 and cisplatin/etoposide was accompanied by central necrosis in several of the enlarged lymph nodes and hepatic metastases, which may have been evidence of pseudoprogression, accounting for her ongoing longer-than-expected survival, since the necrotic tissue may have primed the activity of the PD-1 inhibitor. The lack of response to RRx-001 is hypothesized to have correlated with sparse tumor macrophage infiltration, seen on pre-and post-treatment biopsies, since the mechanism of action of RRx-001 relates to stimulation of tumor-associated macrophages.