Pharmacologic modulation of 5-fluorouracil by folinic acid and pyridoxine for treatment of patients with advanced breast carcinoma.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
31 05 2022
Historique:
received: 19 06 2021
accepted: 12 05 2022
entrez: 31 5 2022
pubmed: 1 6 2022
medline: 3 6 2022
Statut: epublish

Résumé

High concentration pyridoxal 5'-phosphate, the cofactor of vitamin B6, potentiates cytotoxicity in cancer cells exposed to 5-fluorouracil (FUra) and folinic acid (FA). We studied the effect of high-dose pyridoxine on antitumor activity of regimens comprising FUra and FA in 27 advanced breast carcinoma patients. Of 18 previously untreated patients, 12 had tumors that did not overexpress HER2 (Group I), and 6 that overexpressed HER2 (Group II). Nine patients (Group III) had prior chemotherapy. Group I received AVCF (doxorubicin, vinorelbine, cyclophosphamide, FUra, FA) or FAC (doxorubicin, cyclophosphamide, FUra, FA) followed by TCbF (paclitaxel carboplatin, FUra, FA). Groups II, and III received TCbF. Pyridoxine iv (1000-3000 mg/day) preceded each FA and FUra. Group II also received trastuzumab and pertuzumab. 26 patients responded. Three patients in Group I had CRs and 9 had PRs with 62-98% reduction rates; 4 patients in Group II had CRs and 2 had PRs with 98% reduction. Of 7 measurable patients in Group III, 2 attained CRs, and 5 had PRs with 81-94% reduction rates. Median time to response was 3.4 months. Unexpected toxicity did not occur. This pilot study suggests that high-dose vitamin B6 enhances antitumor potency of regimens comprising FUra and FA.

Identifiants

pubmed: 35641554
doi: 10.1038/s41598-022-12998-5
pii: 10.1038/s41598-022-12998-5
pmc: PMC9156777
doi:

Substances chimiques

Doxorubicin 80168379AG
Pyridoxine KV2JZ1BI6Z
Leucovorin Q573I9DVLP
Fluorouracil U3P01618RT

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

9079

Informations de copyright

© 2022. The Author(s).

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Auteurs

David Machover (D)

INSERM U935-UA09 and Institut de Cancérologie et d'Immunogénétique (ICIG), Paul-Brousse Hospital, University Paris-Saclay, 12, Avenue Paul-Vaillant-Couturier, 94800, Villejuif, France. david.machover1@orange.fr.

Emma Goldschmidt (E)

Department of Medical Oncology, Paul-Brousse Hospital, Assistance Publique-Hôpitaux de Paris (APHP), University Paris-Saclay, 94800, Villejuif, France.

Wathek Almohamad (W)

Department of Medical Oncology, Paul-Brousse Hospital, Assistance Publique-Hôpitaux de Paris (APHP), University Paris-Saclay, 94800, Villejuif, France.

Vincent Castagné (V)

Department of Pharmacy, Paul-Brousse Hospital, APHP, University Paris-Saclay, 94800, Villejuif, France.

Julien Dairou (J)

Laboratory of Pharmacologic Biochemistry and Toxicology, CNRS UMR 8601, University Paris-Descartes, 45, Rue des Saints-Pères, 75006, Paris, France.

Christophe Desterke (C)

INSERM U935-UA09 and Institut de Cancérologie et d'Immunogénétique (ICIG), Paul-Brousse Hospital, University Paris-Saclay, 12, Avenue Paul-Vaillant-Couturier, 94800, Villejuif, France.

Léa Gomez (L)

Department of Biophysics and Nuclear Medicine, Kremlin-Bicêtre Hospital, APHP, University Paris-Saclay, 94270, Le Kremlin-Bicêtre, France.

Yann Gaston-Mathé (Y)

YGM Consult SAS, 75015, Paris, France.

Claude Boucheix (C)

INSERM U935-UA09 and Institut de Cancérologie et d'Immunogénétique (ICIG), Paul-Brousse Hospital, University Paris-Saclay, 12, Avenue Paul-Vaillant-Couturier, 94800, Villejuif, France.

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