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Personalized prescription of tyrosine kinase inhibitors in unresectable metastatic cholangiocarcinoma.


ABSTRACT: Background:Cholangiocarcinoma is an aggressive tumor with poor prognosis. Most of the cases are not available for surgery at the stage of the diagnosis and the best clinical practice chemotherapy results in about 12-month median survival. Several tyrosine kinase inhibitors (TKIs) are currently under investigation as an alternative treatment option for cholangiocarcinoma. Thus, the report of personalized selection of effective inhibitor and case outcome are of clinical interest. Case presentation:Here we report a case of aggressive metastatic cholangiocarcinoma (MCC) in 72-year-old man, sequentially treated with two targeted chemotherapies. Initially disease quickly progressed during best clinical practice care (gemcitabine in combination with cisplatin or capecitabine), which was accompanied by significant decrease of life quality. Monotherapy with TKI sorafenib was prescribed to the patient, which resulted in stabilization of tumor growth and elimination of pain. The choice of the inhibitor was made based on high-throughput screening of gene expression in the patient's tumor biopsy, utilized by Oncobox platform to build a personalized rating of potentially effective target therapies. However, time to progression after start of sorafenib administration did not exceed 6 months and the regimen was changed to monotherapy with Pazopanib, another TKI predicted to be effective for this patient according to the same molecular test. It resulted in disease progression according to RECIST with simultaneous elimination of sorafenib side effects such as rash and hand-foot syndrome. After 2 years from the diagnosis of MCC the patient was alive and physically active, which is substantially longer than median survival for standard therapy. Conclusion:This case evidences that sequential personalized prescription of different TKIs may show promising efficacy in terms of survival and quality of life in MCC.

SUBMITTER: Poddubskaya EV 

PROVIDER: S-EPMC6127913 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Personalized prescription of tyrosine kinase inhibitors in unresectable metastatic cholangiocarcinoma.

Poddubskaya Elena V EV   Baranova Madina P MP   Allina Daria O DO   Smirnov Philipp Y PY   Albert Eugene A EA   Kirilchev Alexey P AP   Aleshin Alexey A AA   Sekacheva Marina I MI   Suntsova Maria V MV  

Experimental hematology & oncology 20180906


<h4>Background</h4>Cholangiocarcinoma is an aggressive tumor with poor prognosis. Most of the cases are not available for surgery at the stage of the diagnosis and the best clinical practice chemotherapy results in about 12-month median survival. Several tyrosine kinase inhibitors (TKIs) are currently under investigation as an alternative treatment option for cholangiocarcinoma. Thus, the report of personalized selection of effective inhibitor and case outcome are of clinical interest.<h4>Case p  ...[more]

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