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Clinical Benefit of Sorafenib Combined with Paclitaxel and Carboplatin to a Patient with Metastatic Chemotherapy‐Refractory Testicular Tumors

Testicular cancer is one of the few tumor types that have not yet benefited from targeted therapy. Still no new active agents for treating this cancer have been identified over the past 15 years. Once patients are refractory to cisplatin‐based chemotherapy, they will be expected to die from testicul...

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Autores principales: Lian, Bijun, Zhang, Wenhui, Wang, Tiegong, Yang, Qingsong, Jia, Zepeng, Chen, Huan, Wang, Lei, Xu, Jing, Wang, Wei, Cao, Kai, Gao, Xu, Sun, Yinghao, Shao, Chengwei, Liu, Zhiyong, Li, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6975956/
https://www.ncbi.nlm.nih.gov/pubmed/31492770
http://dx.doi.org/10.1634/theoncologist.2019-0295
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author Lian, Bijun
Zhang, Wenhui
Wang, Tiegong
Yang, Qingsong
Jia, Zepeng
Chen, Huan
Wang, Lei
Xu, Jing
Wang, Wei
Cao, Kai
Gao, Xu
Sun, Yinghao
Shao, Chengwei
Liu, Zhiyong
Li, Jing
author_facet Lian, Bijun
Zhang, Wenhui
Wang, Tiegong
Yang, Qingsong
Jia, Zepeng
Chen, Huan
Wang, Lei
Xu, Jing
Wang, Wei
Cao, Kai
Gao, Xu
Sun, Yinghao
Shao, Chengwei
Liu, Zhiyong
Li, Jing
author_sort Lian, Bijun
collection PubMed
description Testicular cancer is one of the few tumor types that have not yet benefited from targeted therapy. Still no new active agents for treating this cancer have been identified over the past 15 years. Once patients are refractory to cisplatin‐based chemotherapy, they will be expected to die from testicular cancer. This report describes a 21‐year‐old man who was refractory to chemotherapy and immunotherapy. Whole exome sequencing and low‐depth whole genome sequencing confirmed the KRAS gene amplification, which may lead to the tumor cells’ progression and proliferation. After discussion at the molecular tumor board, the patient was offered paclitaxel, carboplatin, and sorafenib (CPS) based on a phase III clinical trial of melanoma with KRAS gene copy gains. After treatment with CPS, the patient achieved excellent curative effects. Because of a nearly 50% frequency of KRAS amplification in chemotherapy‐refractory testicular germ cells, CPS regimen may provide a new therapy, but it still warrants further validation in clinical studies. KEY POINTS. Chemotherapy‐refractory testicular cancer has a very poor prognosis resulting in a lack of effective targeted therapies. KRAS gene amplification occurs in nearly 20% of testicular cancer and 50% of chemotherapy‐refractory testicular cancer. KRAS amplification may activate the MAPK signaling pathway, and inhibition of MAPK by sorafenib combined with paclitaxel and carboplatin could be a viable option based on a phase III clinical trial of melanoma. To the authors’ knowledge, this is the first report of response to sorafenib‐based combination targeted therapy in a patient with chemotherapy‐refractory testicular cancer. Clinical genomic profiling can confirm copy number variation of testicular cancer and provide insights on therapeutic options.
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spelling pubmed-69759562020-01-23 Clinical Benefit of Sorafenib Combined with Paclitaxel and Carboplatin to a Patient with Metastatic Chemotherapy‐Refractory Testicular Tumors Lian, Bijun Zhang, Wenhui Wang, Tiegong Yang, Qingsong Jia, Zepeng Chen, Huan Wang, Lei Xu, Jing Wang, Wei Cao, Kai Gao, Xu Sun, Yinghao Shao, Chengwei Liu, Zhiyong Li, Jing Oncologist Precision Medicine Clinic: Molecular Tumor Board Testicular cancer is one of the few tumor types that have not yet benefited from targeted therapy. Still no new active agents for treating this cancer have been identified over the past 15 years. Once patients are refractory to cisplatin‐based chemotherapy, they will be expected to die from testicular cancer. This report describes a 21‐year‐old man who was refractory to chemotherapy and immunotherapy. Whole exome sequencing and low‐depth whole genome sequencing confirmed the KRAS gene amplification, which may lead to the tumor cells’ progression and proliferation. After discussion at the molecular tumor board, the patient was offered paclitaxel, carboplatin, and sorafenib (CPS) based on a phase III clinical trial of melanoma with KRAS gene copy gains. After treatment with CPS, the patient achieved excellent curative effects. Because of a nearly 50% frequency of KRAS amplification in chemotherapy‐refractory testicular germ cells, CPS regimen may provide a new therapy, but it still warrants further validation in clinical studies. KEY POINTS. Chemotherapy‐refractory testicular cancer has a very poor prognosis resulting in a lack of effective targeted therapies. KRAS gene amplification occurs in nearly 20% of testicular cancer and 50% of chemotherapy‐refractory testicular cancer. KRAS amplification may activate the MAPK signaling pathway, and inhibition of MAPK by sorafenib combined with paclitaxel and carboplatin could be a viable option based on a phase III clinical trial of melanoma. To the authors’ knowledge, this is the first report of response to sorafenib‐based combination targeted therapy in a patient with chemotherapy‐refractory testicular cancer. Clinical genomic profiling can confirm copy number variation of testicular cancer and provide insights on therapeutic options. John Wiley & Sons, Inc. 2019-09-06 2019-12 /pmc/articles/PMC6975956/ /pubmed/31492770 http://dx.doi.org/10.1634/theoncologist.2019-0295 Text en © 2019 The Authors. The Oncologist published by Wiley Periodicals, Inc. on behalf of AlphaMed Press. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Precision Medicine Clinic: Molecular Tumor Board
Lian, Bijun
Zhang, Wenhui
Wang, Tiegong
Yang, Qingsong
Jia, Zepeng
Chen, Huan
Wang, Lei
Xu, Jing
Wang, Wei
Cao, Kai
Gao, Xu
Sun, Yinghao
Shao, Chengwei
Liu, Zhiyong
Li, Jing
Clinical Benefit of Sorafenib Combined with Paclitaxel and Carboplatin to a Patient with Metastatic Chemotherapy‐Refractory Testicular Tumors
title Clinical Benefit of Sorafenib Combined with Paclitaxel and Carboplatin to a Patient with Metastatic Chemotherapy‐Refractory Testicular Tumors
title_full Clinical Benefit of Sorafenib Combined with Paclitaxel and Carboplatin to a Patient with Metastatic Chemotherapy‐Refractory Testicular Tumors
title_fullStr Clinical Benefit of Sorafenib Combined with Paclitaxel and Carboplatin to a Patient with Metastatic Chemotherapy‐Refractory Testicular Tumors
title_full_unstemmed Clinical Benefit of Sorafenib Combined with Paclitaxel and Carboplatin to a Patient with Metastatic Chemotherapy‐Refractory Testicular Tumors
title_short Clinical Benefit of Sorafenib Combined with Paclitaxel and Carboplatin to a Patient with Metastatic Chemotherapy‐Refractory Testicular Tumors
title_sort clinical benefit of sorafenib combined with paclitaxel and carboplatin to a patient with metastatic chemotherapy‐refractory testicular tumors
topic Precision Medicine Clinic: Molecular Tumor Board
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6975956/
https://www.ncbi.nlm.nih.gov/pubmed/31492770
http://dx.doi.org/10.1634/theoncologist.2019-0295
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