Brzezniak Christina, Oronsky Bryan, Trepel Jane, Summers Thomas A, Cabrales Pedro, Lee Min-Jung, Day Regina, Jha Saheli, Caroen Scott, Zeman Karen, Ferry Lindsey, Harmer Cindy, Oronsky Neil, Lybeck Michelle, Lybeck Harry E, Brown James F, Reid Tony R, Carter Corey A
aWalter Reed National Medical Center, Bethesda, MD, USA.
bEpicentRx, San Diego, CA, USA.
Case Rep Oncol. 2017 Mar 29;10(1):276-280. doi: 10.1159/000464101. eCollection 2017 Jan-Apr.
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.
阴道小细胞癌很罕见，实际上在英文期刊上报道的病例总数不到30例。由于发病率极低，尚未制定具体的治疗指南，临床上已知的大部分信息都来自少数单病例报告。然而，鉴于其具有高度侵袭性的组织学特征，类似于小细胞肺癌（SCLC），一线治疗方案是以SCLC为蓝本制定的。本文报道了一例51岁的非裔美国患者，经活检证实为转移性阴道小细胞癌，该患者历经多种治疗：一线使用顺铂和依托泊苷（使其对铂耐药）及放疗，随后在一项名为“四重威胁”的临床试验中使用肿瘤巨噬细胞刺激剂RRx - 001，根据方案，在强制再次使用顺铂和依托泊苷之前使用该药。按照RECIST v.1.1标准，RRx - 001和顺铂/依托泊苷治疗时肿瘤均进展，同时在几个增大的淋巴结和肝转移灶中出现中央坏死，这可能是假性进展的证据，解释了她存活时间长于预期的原因，因为坏死组织可能启动了PD - 1抑制剂的活性。据推测，对RRx - 001无反应与治疗前后活检中观察到的肿瘤巨噬细胞浸润稀疏有关，因为RRx - 001的作用机制与刺激肿瘤相关巨噬细胞有关。
