Detection of trifluridine in tumors of patients with metastatic colorectal cancer treated with trifluridine/tipiracil.
Anti-BrdU antibody
Liver metastasis
Peritoneal dissemination
TAS-102)
Trifluridine (FTD)
Trifluridine/tipiracil (FTD/TPI
Journal
Cancer chemotherapy and pharmacology
ISSN: 1432-0843
Titre abrégé: Cancer Chemother Pharmacol
Pays: Germany
ID NLM: 7806519
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
28
11
2019
accepted:
04
04
2020
pubmed:
24
4
2020
medline:
16
2
2021
entrez:
24
4
2020
Statut:
ppublish
Résumé
Trifluridine (FTD) is the active component of the nucleoside chemotherapeutic drug trifluridine/tipiracil (FTD/TPI), which is approved worldwide for the treatment of patients with metastatic gastrointestinal cancer. FTD exerts cytotoxic effects via its incorporation into DNA, but FTD has not been detected in the tumor specimens of patients. The purpose of this study was to detect FTD in tumors resected from metastatic colorectal cancer (mCRC) patients who were administered FTD/TPI. Another purpose was to investigate the turnover rate of FTD in tumors and bone marrow in a mouse model. Tumors and normal tissue specimens were obtained from mCRC patients who were administered FTD/TPI or placebo at Kyushu University Hospital. Tumors and bone marrow were resected from mice with peritoneal dissemination treated with FTD/TPI. To detect and quantitate FTD incorporated into DNA, immunohistochemical staining of paraffin-embedded specimens (IHC-p staining) and slot-blot analysis of DNA purified from these tissues were performed using an anti-BrdU antibody. IHC-p staining of proliferation and apoptosis markers was also performed. FTD was detected in metastatic tumors obtained from mCRC patients who were administered FTD/TPI, but who had discontinued the treatment several weeks before surgery. In a peritoneal dissemination mouse model, FTD was still detected in tumors 13 days after the cessation of FTD/TPI treatment, but had disappeared from bone marrow within 6 days. These results indicate that FTD persists longer in tumors than in bone marrow, which may cause a sustained antitumor effect with tolerable hematotoxicity.
Identifiants
pubmed: 32322913
doi: 10.1007/s00280-020-04072-6
pii: 10.1007/s00280-020-04072-6
doi:
Substances chimiques
Drug Combinations
0
Pyrrolidines
0
trifluridine tipiracil drug combination
0
Thymine
QR26YLT7LT
Trifluridine
RMW9V5RW38
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1029-1038Références
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