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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: S. Karger AG 2017
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.
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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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