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...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Karger Publishers
2017-03-01
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| Series: | Case Reports in Oncology |
| Subjects: | |
| Online Access: | http://www.karger.com/Article/FullText/464101 |
| _version_ | 1828332244092059648 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Christina Brzezniak |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-13T21:03:36Z |
| format | Article |
| id | doaj.art-5575e28cae354bda83234f8bdd054988 |
| institution | Directory Open Access Journal |
| issn | 1662-6575 |
| language | English |
| last_indexed | 2024-04-13T21:03:36Z |
| publishDate | 2017-03-01 |
| publisher | Karger Publishers |
| record_format | Article |
| series | Case Reports in Oncology |
| spelling | doaj.art-5575e28cae354bda83234f8bdd0549882022-12-22T02:30:04ZengKarger PublishersCase Reports in Oncology1662-65752017-03-0110127628010.1159/000464101464101RRx-001 Priming of PD-1 Inhibition in the Treatment of Small Cell Carcinoma of the Vagina: A Rare Gynecological TumorChristina BrzezniakBryan OronskyJane TrepelThomas A. Summers Jr.Pedro CabralesMin-Jung LeeRegina DaySaheli JhaScott CaroenKaren ZemanLindsey FerryCindy HarmerNeil OronskyMichelle LybeckHarry E. LybeckJames F. BrownTony R. ReidCorey A. CarterSmall 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.http://www.karger.com/Article/FullText/464101Small cell carcinomaVaginaTumor-associated macrophage stimulationImmunotherapyChemotherapyPseudoprogressionRRx-001 |
| spellingShingle | 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 RRx-001 Priming of PD-1 Inhibition in the Treatment of Small Cell Carcinoma of the Vagina: A Rare Gynecological Tumor Case Reports in Oncology Small cell carcinoma Vagina Tumor-associated macrophage stimulation Immunotherapy Chemotherapy Pseudoprogression RRx-001 |
| 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 | Small cell carcinoma Vagina Tumor-associated macrophage stimulation Immunotherapy Chemotherapy Pseudoprogression RRx-001 |
| url | http://www.karger.com/Article/FullText/464101 |
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