A correlation study of fluorouracil pharmacodynamics with clinical efficacy and toxicity

Abstract

based on body surface area (BSA). However, 5-FU has a narrow therapeutic index and high variance (4). These individual differences in plasma levels depend on genetic diversity in the metabolic enzymes of 5-FU (i.e., dihydropyrimidine dehydrogenase [DPD]), as well as kinetic changes related to age, sex, body weight, and dietary differences (5, 6). Previous reports showed that inappropriate dosing is related to increased toxicity and increased rates of unresponsiveness (5, 7). Pharmacokinetic (PK) adjusted doses may overcome the problems of variability (8-11). Area under the target curve of 20-25 mg × h/L was proposed as the valid 5-FU level to achieve clinically effective and less toxic chemotherapy cycles (12-14). However, with BSA-based dosing, only 20%-30% of patients received the valid area under the curve (AUC) dose, whereas nearly 50% of patients were underdosed and 20% were overdosed (8). Gamelin et al suggested increasing the overall response rate from 18% to 33% by PK dosing (14). In this study, we prospectively investigated the clinical benefit and toxicity of 5-FU in relation to pharmacokinetic properties in advanced colorectal cancer and in the adjuvant setting.

Chemotherapy-Induced Neuropathy and Diabetes: A Scoping Review

“…All grades: 0.6-7% [27,28] or 12.9% [29] Grade 3-4: 0% [29] Uncertain [30] High doses and use of 5-FU in combined treatment, increase the risk of neuropathy [31] Gemcitabine All grades: 6% [32] -Methotrexate All grades: 3-10% [31] -…”

Tumor-Selective Immune-Active Mild Hyperthermia Associated with Chemotherapy in Colon Peritoneal Metastasis by Photoactivation of Fluorouracil–Gold Nanoparticle Complexes

“…Among the standard of care chemotherapeutic drugs, 5-FU, a cell proliferation inhibitor, is part of the clinical treatment regime for CRC patients . However, its low solubility is detrimental to its efficacy in addition to the already known systemic side effects . Therefore, there is a need for building robust nanosystems that allow the proper delivery of 5-FU to the tumors, preventing the systemic toxicity and assuring the local therapeutic effect.…”

“…Drug regimens for HIPEC may include platinum-based agents (cisplatin, oxaliplatin, or carboplatin), mitomycin, doxorubicin, paclitaxel, and 5-fluorouracil (5-FU). , 5-FU is a fluorinated pyrimidine analogue that blocks DNA synthesis, eliciting a broad-spectrum anticancer effect . However, 5-FU’s short half-life and systemic toxicity (such as hair thinning, hematological disorders, and bone marrow dysfunction, skin rash, and, in some cases, serious gastro-intestinal morbidities) cause severe discomfort in patients. , Due to the rather short half-life and the systemic toxicity of 5-FU, we choose this drug as a model to demonstrate whether its complexation with gold nanoparticles can overcome these setbacks through its stabilization in biological fluids. The nanovectorization of drugs has the potential to diminish the toxicity of chemotherapy to healthy tissue.…”

“…33 However, 5-FU's short half-life and systemic toxicity (such as hair thinning, hematological disorders, and bone marrow dysfunction, skin rash, and, in some cases, serious gastro-intestinal morbidities) cause severe discomfort in patients. 34,35 Due to the rather short half-life and the systemic toxicity of 5-FU, we choose this drug as a model to demonstrate whether its complexation with gold nanoparticles can overcome these setbacks through its stabilization in biological fluids. The nanovectorization of drugs has the potential to diminish the toxicity of chemotherapy to healthy tissue.…”

Dauricine suppresses the growth of pancreatic cancer in�vivo by modulating the Hedgehog signaling pathway

“…However, it is associated with several side effects, including mouth sores, anorexia, nausea, vomiting, diarrhea, photophobia, leukocytopenia, erythrocytopenia and thrombocytopenia (41). These side effects increase the risk of infection, bleeding and anemia (42). In the present study, 5-FU was selected as the positive control for the evaluation of the effects of dauricine.…”