Pharmacologic modulation of 5-fluorouracil by folinic acid and high-dose pyridoxine for treatment of patients with digestive tract carcinomas

Abstract Supplementation of cancer cells exposed to 5-fluorouracil (FUra) and folinic acid (FA) with high concentration pyridoxal 5′-phosphate, the cofactor of vitamin B6, potentiates the cytotoxicity of FUra in a synergistic interaction mode. We report a pilot study in 13 patients with previously u...

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Autores principales:	David Machover, Wathek Almohamad, Vincent Castagné, Christophe Desterke, Léa Gomez, Yann Gaston-Mathé, Claude Boucheix, Emma Goldschmidt
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e48a6dffbe93495e979f8eb33857f074
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spelling	oai:doaj.org-article:e48a6dffbe93495e979f8eb33857f0742021-12-02T17:41:05ZPharmacologic modulation of 5-fluorouracil by folinic acid and high-dose pyridoxine for treatment of patients with digestive tract carcinomas10.1038/s41598-021-92110-52045-2322https://doaj.org/article/e48a6dffbe93495e979f8eb33857f0742021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92110-5https://doaj.org/toc/2045-2322Abstract Supplementation of cancer cells exposed to 5-fluorouracil (FUra) and folinic acid (FA) with high concentration pyridoxal 5′-phosphate, the cofactor of vitamin B6, potentiates the cytotoxicity of FUra in a synergistic interaction mode. We report a pilot study in 13 patients with previously untreated advanced carcinoma of the digestive tract to assess the impact of high-dose pyridoxine (PN) on the antitumor activity of regimens comprising FUra and FA. Five patients had colorectal adenocarcinoma (CRC); 5 had pancreas adenocarcinoma (PC); and 3 had squamous cell carcinoma of the esophagus (EC). Patients with CRC and with PC received oxaliplatin, irinotecan, FUra and FA, and patients with EC had paclitaxel, carboplatin, FUra and FA. PN iv from 1000 to 3000 mg/day preceded each administration of FA and FUra. Eleven patients responded. Two patients with CRC attained CRs and 3 had PRs with reduction rates ≥ 78%. Two patients with PC attained CRs, and 2 had PRs with reduction rates ≥ 79%. Responders experienced disappearance of most metastases. Of 3 patients with EC, 2 attained CRs. Median time to attain a response was 3 months. Unexpected toxicity did not occur. Results suggest that high-dose vitamin B6 enhances antitumor potency of regimens comprising FUra and FA.David MachoverWathek AlmohamadVincent CastagnéChristophe DesterkeLéa GomezYann Gaston-MathéClaude BoucheixEmma GoldschmidtNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q David Machover Wathek Almohamad Vincent Castagné Christophe Desterke Léa Gomez Yann Gaston-Mathé Claude Boucheix Emma Goldschmidt Pharmacologic modulation of 5-fluorouracil by folinic acid and high-dose pyridoxine for treatment of patients with digestive tract carcinomas
description	Abstract Supplementation of cancer cells exposed to 5-fluorouracil (FUra) and folinic acid (FA) with high concentration pyridoxal 5′-phosphate, the cofactor of vitamin B6, potentiates the cytotoxicity of FUra in a synergistic interaction mode. We report a pilot study in 13 patients with previously untreated advanced carcinoma of the digestive tract to assess the impact of high-dose pyridoxine (PN) on the antitumor activity of regimens comprising FUra and FA. Five patients had colorectal adenocarcinoma (CRC); 5 had pancreas adenocarcinoma (PC); and 3 had squamous cell carcinoma of the esophagus (EC). Patients with CRC and with PC received oxaliplatin, irinotecan, FUra and FA, and patients with EC had paclitaxel, carboplatin, FUra and FA. PN iv from 1000 to 3000 mg/day preceded each administration of FA and FUra. Eleven patients responded. Two patients with CRC attained CRs and 3 had PRs with reduction rates ≥ 78%. Two patients with PC attained CRs, and 2 had PRs with reduction rates ≥ 79%. Responders experienced disappearance of most metastases. Of 3 patients with EC, 2 attained CRs. Median time to attain a response was 3 months. Unexpected toxicity did not occur. Results suggest that high-dose vitamin B6 enhances antitumor potency of regimens comprising FUra and FA.
format	article
author	David Machover Wathek Almohamad Vincent Castagné Christophe Desterke Léa Gomez Yann Gaston-Mathé Claude Boucheix Emma Goldschmidt
author_facet	David Machover Wathek Almohamad Vincent Castagné Christophe Desterke Léa Gomez Yann Gaston-Mathé Claude Boucheix Emma Goldschmidt
author_sort	David Machover
title	Pharmacologic modulation of 5-fluorouracil by folinic acid and high-dose pyridoxine for treatment of patients with digestive tract carcinomas
title_short	Pharmacologic modulation of 5-fluorouracil by folinic acid and high-dose pyridoxine for treatment of patients with digestive tract carcinomas
title_full	Pharmacologic modulation of 5-fluorouracil by folinic acid and high-dose pyridoxine for treatment of patients with digestive tract carcinomas
title_fullStr	Pharmacologic modulation of 5-fluorouracil by folinic acid and high-dose pyridoxine for treatment of patients with digestive tract carcinomas
title_full_unstemmed	Pharmacologic modulation of 5-fluorouracil by folinic acid and high-dose pyridoxine for treatment of patients with digestive tract carcinomas
title_sort	pharmacologic modulation of 5-fluorouracil by folinic acid and high-dose pyridoxine for treatment of patients with digestive tract carcinomas
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e48a6dffbe93495e979f8eb33857f074
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Pharmacologic modulation of 5-fluorouracil by folinic acid and high-dose pyridoxine for treatment of patients with digestive tract carcinomas

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