Fluorouracil, Capecitabine (Dosage)

Fluoropyrimidines are a family of chemotherapeutic drugs widely used in cancer treatment. Between 10 and 40% of individuals treated with these drugs develop adverse effects and this has been associated with the presence of certain variants in the DPYD gene, directly involved in their metabolism.

The family of antineoplastic drugs known as fluoropyrimidines (fluorouracil, capecitabine, tegafur, among others) is composed of chemotherapeutic agents that are widely used in the treatment of different types of cancers. They belong to a family of antineoplastic drugs called antimetabolites. The most serious side effects that fluoropyrimidines can cause are neurotoxicity and bone marrow suppression.

Fluorouracil, which is often called 5FU, is used to treat different types of cancer such as breast, bowel, skin, stomach, esophagus (throat) and pancreatic cancer. The most common side effects of fluorouracil are: infections, bleeding, anemia, nausea, diarrhea, loss of appetite, mouth pain, taste alterations, tiredness, tingling of hands and feet, hair loss, changes in heart rhythm. Other less common side effects of fluorouracil are: eye pain, skin sensitivity causing pain, risk of blood clots (symptoms are pain, redness and swelling in extremities, shortness of breath and chest pain), neurotoxicity, bone marrow suppression.

Capecitabine is used as chemotherapy to treat metastatic colon or rectal cancer and metastatic breast cancer. It is a prodrug of fluoruracil, i.e. it is converted to fluoruracil in the body. The most common side effects of capecitabine treatment, with an incidence greater than 30%, are: anemia, fatigue, diarrhea, Hand and foot syndrome (palmar-plantar erythrodysesthesia or PPE, which presents with rash, swelling, redness, pain and/or peeling of the skin on the palms of the hands and soles of the feet. It is usually mild and begins 2 weeks after initiation of treatment. May require a reduction in drug dose), nausea and vomiting, dermatitis, elevated liver enzymes, increased bilirubin. Other less frequent side effects (incidence between 10-29%) are: poco apetito, dolor abdominal, infecciones, hemorragias, estreñimiento, fiebre, disnea, dolor en el pecho, insomnio, coágulos sanguíneos, somnolencia excesiva, confusión, convulsions, loss of balance, nail changes, darkening of the skin, neurotoxicity, bone marrow suppression.

BRAND NAMES

  • Fluorouracil: Efudex®, Adrucil®, Carac®, Fluoroplex®.
  • Capecitabine: Xeloda®

Genes analyzed

DPYD

Bibliography

Amstutz U, Henricks LM, Offer SM, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing: 2017 Update. Clin Pharmacol Ther. 2018 Feb;103(2):210-216.

Lunenburg CATC, van der Wouden CH, Nijenhuis M, et al.Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction of DPYD and fluoropyrimidines. Eur J Hum Genet. 2020 Apr;28(4):508-517.

Maillard M, Launay M, Royer B, et al. Quantitative impact of pre-analytical process on plasma uracil when testing for dihydropyrimidine dehydrogenase deficiency. Br J Clin Pharmacol. 2023 Feb;89(2):762-772.

Maslarinou A, Manolopoulos VG, Ragia G.Pharmacogenomic-guided dosing of fluoropyrimidines beyond DPYD: time for a polygenic algorithm? Front Pharmacol. 2023 May 15;14:1184523.

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