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RRx-001 Priming of PD-1 Inhibition in the Treatment of Small Cell Carcinoma of the Vagina: A Rare Gynecological Tumor
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 sing...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
S. Karger AG
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5422722/ https://www.ncbi.nlm.nih.gov/pubmed/28512410 http://dx.doi.org/10.1159/000464101 |
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author | Brzezniak, Christina Oronsky, Bryan Trepel, Jane Summers Jr., 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. |
author_facet | Brzezniak, Christina Oronsky, Bryan Trepel, Jane Summers Jr., 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. |
author_sort | Brzezniak, Christina |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5422722 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | S. Karger AG |
record_format | MEDLINE/PubMed |
spelling | pubmed-54227222017-05-16 RRx-001 Priming of PD-1 Inhibition in the Treatment of Small Cell Carcinoma of the Vagina: A Rare Gynecological Tumor Brzezniak, Christina Oronsky, Bryan Trepel, Jane Summers Jr., 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. Case Rep Oncol Case Report 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. S. Karger AG 2017-03-29 /pmc/articles/PMC5422722/ /pubmed/28512410 http://dx.doi.org/10.1159/000464101 Text en Copyright © 2017 by S. Karger AG, Basel http://creativecommons.org/licenses/by-nc/4.0/ This article is licensed under the Creative Commons Attribution-NonCommercial-4.0 International License (CC BY-NC) (http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes requires written permission. |
spellingShingle | Case Report Brzezniak, Christina Oronsky, Bryan Trepel, Jane Summers Jr., 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. RRx-001 Priming of PD-1 Inhibition in the Treatment of Small Cell Carcinoma of the Vagina: A Rare Gynecological Tumor |
title | RRx-001 Priming of PD-1 Inhibition in the Treatment of Small Cell Carcinoma of the Vagina: A Rare Gynecological Tumor |
title_full | RRx-001 Priming of PD-1 Inhibition in the Treatment of Small Cell Carcinoma of the Vagina: A Rare Gynecological Tumor |
title_fullStr | RRx-001 Priming of PD-1 Inhibition in the Treatment of Small Cell Carcinoma of the Vagina: A Rare Gynecological Tumor |
title_full_unstemmed | RRx-001 Priming of PD-1 Inhibition in the Treatment of Small Cell Carcinoma of the Vagina: A Rare Gynecological Tumor |
title_short | RRx-001 Priming of PD-1 Inhibition in the Treatment of Small Cell Carcinoma of the Vagina: A Rare Gynecological Tumor |
title_sort | rrx-001 priming of pd-1 inhibition in the treatment of small cell carcinoma of the vagina: a rare gynecological tumor |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5422722/ https://www.ncbi.nlm.nih.gov/pubmed/28512410 http://dx.doi.org/10.1159/000464101 |
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