Pharmacologic modulation of 5-fluorouracil by folinic acid and pyridoxine for treatment of patients with advanced breast carcinoma
Abstract 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 breas...
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| Format: | Article |
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Nature Portfolio
2022-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-12998-5 |
| _version_ | 1818202855837794304 |
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| author | David Machover Emma Goldschmidt Wathek Almohamad Vincent Castagné Julien Dairou Christophe Desterke Léa Gomez Yann Gaston-Mathé Claude Boucheix |
| author_facet | David Machover Emma Goldschmidt Wathek Almohamad Vincent Castagné Julien Dairou Christophe Desterke Léa Gomez Yann Gaston-Mathé Claude Boucheix |
| author_sort | David Machover |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-12T03:16:05Z |
| format | Article |
| id | doaj.art-dd474b15951249689b5f3b8a1a546569 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-12T03:16:05Z |
| publishDate | 2022-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-dd474b15951249689b5f3b8a1a5465692022-12-22T00:40:17ZengNature PortfolioScientific Reports2045-23222022-05-0112111410.1038/s41598-022-12998-5Pharmacologic modulation of 5-fluorouracil by folinic acid and pyridoxine for treatment of patients with advanced breast carcinomaDavid Machover0Emma Goldschmidt1Wathek Almohamad2Vincent Castagné3Julien Dairou4Christophe Desterke5Léa Gomez6Yann Gaston-Mathé7Claude Boucheix8INSERM U935-UA09 and Institut de Cancérologie et d’Immunogénétique (ICIG), Paul-Brousse Hospital, University Paris-SaclayDepartment of Medical Oncology, Paul-Brousse Hospital, Assistance Publique-Hôpitaux de Paris (APHP), University Paris-SaclayDepartment of Medical Oncology, Paul-Brousse Hospital, Assistance Publique-Hôpitaux de Paris (APHP), University Paris-SaclayDepartment of Pharmacy, Paul-Brousse Hospital, APHP, University Paris-SaclayLaboratory of Pharmacologic Biochemistry and Toxicology, CNRS UMR 8601, University Paris-DescartesINSERM U935-UA09 and Institut de Cancérologie et d’Immunogénétique (ICIG), Paul-Brousse Hospital, University Paris-SaclayDepartment of Biophysics and Nuclear Medicine, Kremlin-Bicêtre Hospital, APHP, University Paris-SaclayYGM Consult SASINSERM U935-UA09 and Institut de Cancérologie et d’Immunogénétique (ICIG), Paul-Brousse Hospital, University Paris-SaclayAbstract 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.https://doi.org/10.1038/s41598-022-12998-5 |
| spellingShingle | David Machover Emma Goldschmidt Wathek Almohamad Vincent Castagné Julien Dairou Christophe Desterke Léa Gomez Yann Gaston-Mathé Claude Boucheix Pharmacologic modulation of 5-fluorouracil by folinic acid and pyridoxine for treatment of patients with advanced breast carcinoma Scientific Reports |
| title | Pharmacologic modulation of 5-fluorouracil by folinic acid and pyridoxine for treatment of patients with advanced breast carcinoma |
| title_full | Pharmacologic modulation of 5-fluorouracil by folinic acid and pyridoxine for treatment of patients with advanced breast carcinoma |
| title_fullStr | Pharmacologic modulation of 5-fluorouracil by folinic acid and pyridoxine for treatment of patients with advanced breast carcinoma |
| title_full_unstemmed | Pharmacologic modulation of 5-fluorouracil by folinic acid and pyridoxine for treatment of patients with advanced breast carcinoma |
| title_short | Pharmacologic modulation of 5-fluorouracil by folinic acid and pyridoxine for treatment of patients with advanced breast carcinoma |
| title_sort | pharmacologic modulation of 5 fluorouracil by folinic acid and pyridoxine for treatment of patients with advanced breast carcinoma |
| url | https://doi.org/10.1038/s41598-022-12998-5 |
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