Controlling serum uric acid using febuxostat in cancer patients at risk of tumor lysis syndrome

Takai, Mihoko; Yamauchi, Takahiro; Fujita, Kazuo; Lee, Shin; Ookura, Miyuki; Kishi, Shinji; Urasaki, Yoshimasa; Yoshida, Akira; Iwasaki, Hiromichi; Ueda, Takanori

doi:10.3892/ol.2014.2394

Cited by 17 publications

(11 citation statements)

References 27 publications

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“…Recently, several studies have been conducted to examine the FBX anti-cancer activity [ 16 , 42 , 43 ], with particular regard to its ability to enhance cancer cells death via apoptosis and decrease the chemotherapy resistance, then representing a promising candidate for cancer treatment. Additionally, based on its ability to reduce uric acid production in the body, this drug has been used for the treatment of tumor lysis syndrome, a metabolic impairment that arises in cancer patients [ 15 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

The Encapsulation of Febuxostat into Emulsomes Strongly Enhances the Cytotoxic Potential of the Drug on HCT 116 Colon Cancer Cells

et al. 2020

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Febuxostat (FBX) is a drug able to inhibit xanthine oxidase and reduce uric acid production commonly used for the treatment of hyperuricemia in subjects suffering from gout. Several studies have also been directed at its use as anti-cancer drug during the last years, opening a window for its off-label use. In the present study, an optimized formulation in terms of vesicle size and drug release, obtained by encapsulation of FBX into the emulsomes (FBX-EMLs), was evaluated for its cytotoxic potential in human colorectal carcinoma (HCT 116) cells. The optimized FBX-EMLs formula had an improved half maximal inhibitory concentration (IC50), about 4-fold lower, compared to the free drug. The cell cycle analysis showed a significant inhibition of the HCT 116 cells proliferation following FBX-EMLs treatment compared to all the other conditions, with a higher number of cells accumulating on G2/M and pre-G1 phases, paralleled by a significant reduction of cells in G0/G1 and S phases. The optimized formula was also able to significantly increase the percentage of cell population in both early and late stages of apoptosis, characterized by a higher intracellular caspase-3 concentration, as well as percentage of necrotic cells. Lastly, the FBX ability to decrease the mitochondrial membrane potential was enhanced when the drug was delivered into the EMLs. In conclusion, the new formulation of FBX into EMLs improved all the parameters related to the anti-proliferative activity and the toxic potential of the drug towards colorectal cancer cells.

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Section: Discussionmentioning

confidence: 99%

The Encapsulation of Febuxostat into Emulsomes Strongly Enhances the Cytotoxic Potential of the Drug on HCT 116 Colon Cancer Cells

et al. 2020

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“…One study was excluded after reading the full text, as it was considered as a partial duplicate of another study already included in the present review.…”

Section: Resultsmentioning

confidence: 99%

Febuxostat administration for the prevention of tumour lysis syndrome: A meta‐analysis

et al. 2019

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Summary What is known and objective Tumour lysis syndrome is an oncological emergency, characterized by rapid cytolysis leading to an abrupt rise of serum uric acid levels. The aim of the present meta‐analysis is to evaluate the efficacy and safety of febuxostat as a preventive measure in patients at risk of tumour lysis syndrome development, by comparing it with allopurinol administration. Methods MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov and Google Scholar databases were searched from inception to 15 December 2018. All studies evaluating the effectiveness of febuxostat in preventing tumour lysis syndrome were held eligible. Results and Discussion Six studies were included with a total of 658 patients. Compared to allopurinol, febuxostat achieved a similar response rate (OR: 1.39, 95% CI: [0.55, 3.51]) and tumour lysis syndrome incidence (OR: 1.01, 95% CI: [0.56, 1.81]). Serum uric acid levels did not differ between the investigated groups at the second (MD: −0.21 mg/dL, 95% CI: [−1.30, 0.88]) and seventh (MD: −0.43 mg/dL, 95% CI: [−1.38, 0.51]) day of treatment. Elevation of liver function tests was the most common adverse effect, although its incidence was similar among patients treated with allopurinol and febuxostat. What is new and conclusions The present meta‐analysis suggests that febuxostat may serve as an effective alternative to allopurinol in the prevention of tumour lysis syndrome. Future large‐scale studies should define the optimal febuxostat dosage, explore the most appropriate population for its administration and better define its safety profile.

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“…6 The CPIC guidelines currently recommend that allopurinol should not be prescribed to patients who are carriers of HLA-B*58:01 and that an alternative therapy be used, such as febuxostat. [41][42][43] For individuals who are not HLA-B*58:01 carriers, the use of standard dosing of allopurinol is recommended. 41…”

Section: Allopurinolmentioning

confidence: 99%

Pharmacogenomics in Asian Subpopulations and Impacts on Commonly Prescribed Medications

Nguyen

Yang

et al. 2020

Clinical Translational Sci

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Asians as a group comprise > 60% the world’s population. There is an incredible amount of diversity in Asian and admixed populations that has not been addressed in a pharmacogenetic context. The known pharmacogenetic differences in Asian subgroups generally represent previously known variants that are present at much lower or higher frequencies in Asians compared with other populations. In this review we summarize the main drugs and known genes that appear to have differences in their pharmacogenetic properties in certain Asian populations. Evidence‐based guidelines and summary statistics from the US Food and Drug Administration and the Clinical Pharmacogenetics Implementation Consortium were analyzed for ethnic differences in outcomes. Implicated drugs included commonly prescribed drugs such as warfarin, clopidogrel, carbamazepine, and allopurinol. The majority of these associations are due to Asians more commonly being poor metabolizers of cytochrome P450 (CYP) 2C19 and carriers of the human leukocyte antigen (HLA)‐B*15:02 allele. The relative risk increase was shown to vary between genes and drugs, but could be > 100‐fold higher in Asians. Specifically, there was a 172‐fold increased risk of Stevens‒Johnson syndrome and toxic epidermal necrolysis with carbamazepine use among HLA‐B*15:02 carriers. The effects ranged from relatively benign reactions such as reduced drug efficacy to severe cutaneous skin reactions. These reactions are severe and prevalent enough to warrant pharmacogenetic testing and appropriate changes in dose and medication choice for at‐risk populations. Further studies should be done on Asian cohorts to more fully understand pharmacogenetic variants in these populations and to clarify how such differences may influence drug response.

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Controlling serum uric acid using febuxostat in cancer patients at risk of tumor lysis syndrome

Cited by 17 publications

References 27 publications

The Encapsulation of Febuxostat into Emulsomes Strongly Enhances the Cytotoxic Potential of the Drug on HCT 116 Colon Cancer Cells

The Encapsulation of Febuxostat into Emulsomes Strongly Enhances the Cytotoxic Potential of the Drug on HCT 116 Colon Cancer Cells

Febuxostat administration for the prevention of tumour lysis syndrome: A meta‐analysis

Pharmacogenomics in Asian Subpopulations and Impacts on Commonly Prescribed Medications

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