1. RRx-001 Priming of PD-1 Inhibition in the Treatment of Small Cell Carcinoma of the Vagina: A Rare Gynecological Tumor
- Author
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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, and Carter, Corey A
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Rare Diseases ,Lung ,Lung Cancer ,Orphan Drug ,Cancer ,Small cell carcinoma ,Vagina ,Tumor-associated macrophage stimulation ,Immunotherapy ,Chemotherapy ,Pseudoprogression ,RRx-001 ,Oncology and carcinogenesis - 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.
- Published
- 2017