Therapeutic drug monitoring of 5-fluorouracil

Abstract

Purpose For over 50 years, 5-FU has played a critical role in the systemic chemotherapy of cancer patients. 5-FU serves as the main backbone of combination chemotherapy for patients with colorectal cancer (CRC) in both the adjuvant and metastatic disease settings. Herein, we review the current status of 5-FU therapeutic drug monitoring (TDM) and discuss its potential role in the clinical practice setting. Method PubMed and abstracts from the American Society of Clinical Oncology (ASCO) were searched up through September 2015 for clinical data relating to 5-FU TDM. Results 5-FU dosing has been typically determined by using body surface area (BSA). However, it is now well-established that BSA-based 5-FU dosing is correlated with a wide variation of 5-FU systemic exposure. Pharmacokinetic (PK) studies of 5-FU systemic exposure have shown a wide range of interpatient variation of 5-FU plasma drug levels. Over the past 30 years, increasing efforts have been placed on optimizing 5-FU dosing with the main goals of increasing antitumor efficacy while reducing drug-associated toxicity. There is growing evidence to show that 5-FU dosing based on plasma 5-FU drug level is feasible and that 5-FU TDM can improve clinical outcomes by improving efficacy of 5-FU-based combination regimens and reducing toxicities. Conclusion Dose adjustment of 5-FU is feasible and PK-based dosing can significantly improve clinical outcomes by reducing toxicities and improving efficacy.

Characterization of HIF‐1α/Glycolysis Hyperactive Cell Population via Small‐Molecule‐Based Imaging of Mitochondrial Transporter Activity

“…5‐FU is a critical systemic chemotherapy drug widely used in the treatment of cancer patients including colorectal cancer, gastric cancer, liver cancer, breast cancer, lung cancer, and skin cancer 19. However, the low specificity of 5‐FU to cancer cells leads to severe side effects.…”

Impact of the individualization of the first‑line chemotherapy for advanced colorectal cancer based on collagen gel droplet‑embedded drug sensitivity test

“…Several studies have investigated individualization in 5-FU-based chemotherapy based on the 5-FU metabolism-associated enzymatic and genetic characteristics of the individual patient (22)(23)(24)(25)(26)(27)(28)(29). In addition, the individualization of 5-FU-based chemotherapy based on the serum 5-FU concentration has been reported lately (30)(31)(32)(33)(34). However, individualization in 5-FU-based chemotherapy remains to be implemented in a clinical setting.…”

Inhibition of phosphoserine phosphatase enhances the anticancer efficacy of 5-fluorouracil in colorectal cancer

“…The chemotherapeutic 5-fluorouracil (5-FU) has been widely used in the clinic for treatment of CRC. However, chemotherapy frequently fails in the treatment of CRC, due to development of drug resistance [3,4]. Therefore, it would be beneficial to develop therapeutic strategies that cause CRC cells to regain sensitivity to cytotoxic drugs.…”