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

• Published in: Scientific reports 2022-05, Vol.12 (1), p.9079-9079, Article 9079
• Main Authors: Machover, David, Goldschmidt, Emma, Almohamad, Wathek, Castagné, Vincent, Dairou, Julien, Desterke, Christophe, Gomez, Léa, Gaston-Mathé, Yann, Boucheix, Claude
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil; 631/154; 631/67; 692/4028; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antitumor activity; Breast cancer; Breast carcinoma; Breast Neoplasms - pathology; Carboplatin; Chemotherapy; Cyclophosphamide; Cyclophosphamide - therapeutic use; Cytotoxicity; Doxorubicin; ErbB-2 protein; Female; Fluorouracil - therapeutic use; Folinic acid; Humanities and Social Sciences; Humans; Leucovorin; multidisciplinary; Paclitaxel; Patients; Pilot Projects; Pyridoxine; Pyridoxine - therapeutic use; Science; Science (multidisciplinary); Trastuzumab; Tumors; Vinorelbine; Vitamin B6
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-12998-5

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.