RRx-001 Priming of PD-1 Inhibition in the Treatment of Small Cell Carcinoma of the Vagina: A Rare Gynecological Tumor.

Abstract

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.

• Authors: Christina Brzezniak, Bryan Oronsky, Jane Trepel, Thomas A Summers Jr, Pedro Cabrales, Min-Jung Lee, Regina Day, Saheli Jha, Scott Caroen, Karen Zeman, Lindsey Ferry, Cindy Harmer, Neil Oronsky, Michelle Lybeck, Harry E Lybeck, James F Brown, Tony R Reid, Corey A Carter
• Journal: Case reports in oncology (Case Rep Oncol) 2017 Jan-Apr Vol. 10 Issue 1 Pg. 276-280 ISSN: 1662-6575 [Print] Switzerland
• PMID: 28512410 (Publication Type: Case Reports)