5-Fluorouracil (5-FU) is a chemotherapy medication used in the treatment of various cancers, including colorectal, breast, stomach, and head and neck cancers. It is often administered over a specific, extended period, such as 46 hours, a duration chosen to maximize its therapeutic effect. This prolonged infusion is due to how the drug targets cancer cells and how the body processes it.
How 5-FU Targets Cancer Cells
5-FU functions as an antimetabolite, interfering with the metabolic processes cancer cells need to grow. It closely resembles uracil, a natural building block of ribonucleic acid (RNA), leading cancer cells to mistakenly incorporate 5-FU into their genetic material.
Once inside the cell, 5-FU converts into active forms that disrupt DNA and RNA synthesis. A primary mechanism involves inhibiting thymidylate synthase (TS), an enzyme needed for producing thymidine, a DNA component. This inhibition prevents cancer cells from accurately replicating their DNA and repairing damage.
The drug’s active metabolites can also be incorporated into RNA, creating “fraudulent RNA” that interferes with its normal function and protein production. Cancer cells, especially those that divide rapidly, are vulnerable to 5-FU due to their high demand for DNA and RNA synthesis. The drug primarily targets cells in the S-phase of their cell cycle, when DNA is actively synthesized.
The Body’s Interaction with 5-FU
How the body processes 5-FU influences its administration method. 5-FU has a very short half-life in the bloodstream, typically ranging from 8 to 20 minutes, meaning it is quickly broken down and eliminated.
The enzyme dihydropyrimidine dehydrogenase (DPD) metabolizes a large portion of 5-FU, converting approximately 80% to 85% of the drug into inactive substances. Because 5-FU is cleared quickly, continuous infusion is necessary to maintain a consistent, effective concentration in the bloodstream, ensuring cancer cells are continuously exposed.
Maintaining stable drug levels is important because cancer cells do not all divide simultaneously. Continuous delivery captures more cancer cells as they enter their vulnerable S-phase, maximizing the drug’s cytotoxic effect. This approach compensates for the body’s rapid metabolism, ensuring a therapeutic concentration is present throughout the tumor cells’ growth cycles.
Maximizing Treatment Effectiveness
Administering 5-FU as a prolonged, continuous infusion offers distinct advantages over rapid, single (bolus) injections. Continuous infusion improves tumor response rates; a meta-analysis showed a 22% response rate compared to 14% for bolus administration.
Prolonged exposure allows the drug to affect cancer cells as they progress through their cell cycle, particularly the S-phase, over an extended period. Bolus injections deliver a high concentration quickly, potentially missing cancer cells not in a vulnerable phase.
Continuous infusion leads to a more favorable side effect profile. Bolus administration is associated with more severe myelosuppression, mucositis, and diarrhea. While continuous infusion can increase hand-foot syndrome, it reduces the severity of other common side effects. Continuous infusion also improves overall survival. For patient convenience, prolonged infusions are managed with portable pumps, allowing treatment outside a hospital.