An SNP in CYP39A1 is associated with severe neutropenia induced by docetaxel

Uchiyama, Toshitaka; Kanno, Hitoshi; Ishitani, Ken; Fujii, H.; Ohta, Hiroaki; Kamatani, Naoyuki; Saito, Kayoko

doi:10.1007/s00280-012-1872-4

Cited by 27 publications

(18 citation statements)

References 24 publications

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“…CYP39A1 is one of many CYP enzymes involved in bile acid synthesis from cholesterol [108]. Variants in CYP39A1 have shown a correlation with the incidence of certain adverse toxicities in patients treated with docetaxel [109]. At present further study is required to determine the functional role of CYP39A1 in Bu metabolism and/or treatment-related toxicities and outcomes.…”

Section: Pharmacogenomics Of Busulfan Pkmentioning

confidence: 99%

Clarifying busulfan metabolism and drug interactions to support new therapeutic drug monitoring strategies: a comprehensive review

Myers

Kawedia

Champlin

et al. 2017

Expert Opinion on Drug Metabolism & Toxicology

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Introduction Busulfan (Bu) is an alkylating agent with a limited therapeutic margin and exhibits inter-patient variability in pharmacokinetics (PK). Despite decades of use, mechanisms of Bu PK-based drug-drug interactions (DDIs), as well as the negative downstream effects of these DDIs, have not been fully characterized. Areas covered This article provides an overview of Bu PK, with a primary focus on how known and potentially unknown drug metabolism pathways influence Bu-associated DDIs. In addition, pharmacogenomics of Bu chemotherapy and Bu-related DDIs observed in the stem cell transplant clinic (SCT) are summarized. Finally the increasing importance of Bu therapeutic drug monitoring is highlighted. Expert Opinion Mechanistic studies of Bu metabolism have shown that in addition to GST isoenzymes, other oxidative enzymes (CYP, FMO) and ABC/MDR drug transporters likely contribute to the overall clearance of Bu. Despite many insights, results from clinical studies, especially in polypharmacy settings and between pediatric and adult patients, remain conflicting. Further basic science and clinical investigative efforts are required to fully understand the key factors determining Bu PK characteristics and its effects on complications after SCT. Improved TDM strategies are promising components to further investigate, for instance DDI mechanisms and patient outcomes, in the highly complex SCT treatment setting.

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Section: Pharmacogenomics Of Busulfan Pkmentioning

confidence: 99%

Clarifying busulfan metabolism and drug interactions to support new therapeutic drug monitoring strategies: a comprehensive review

Myers

Kawedia

Champlin

et al. 2017

Expert Opinion on Drug Metabolism & Toxicology

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“…One study reported that simultaneous presence of the CYP3A4*1B and CYP3A5*1A alleles was associated with a 64% increase in docetaxel clearance ( P = 0.0015) . In addition, rs7761731 of CYP39A1 was found to be the only SNP significantly associated ( P = 0.049, OR = 9.0) with the incidence of grade 4 neutropenia among 28 SNP, which were associated with the AUC of docetaxel . The pharmacogenomics of docetaxel have not yet been elucidated in a large clinical study.…”

Section: Pharmacokineticsmentioning

confidence: 99%

“…(36) In addition, rs7761731 of CYP39A1 was found to be the only SNP significantly associated (P = 0.049, OR = 9.0) with the incidence of grade 4 neutropenia among 28 SNP, which were associated with the AUC of docetaxel. (37) The pharmacogenomics of docetaxel have not yet been elucidated in a large clinical study. A genome-wide association study is expected to find genomic variants which relate to the efficacy or toxicity of docetaxel.…”

Section: Pharmacokineticsmentioning

confidence: 99%

Pharmacokinetics, dynamics and toxicity of docetaxel: Why the Japanese dose differs from the Western dose

2015

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Docetaxel (Taxotere®) has been one of the most important chemotherapeutic drugs for cancer treatment since 1996. Although a large number of clinical studies have been conducted in various cancer fields, there is a discrepancy in the standard dose between Japan and Western countries. This article reviews the pharmacokinetic, pharmacodynamic and toxicological profiles of docetaxel, and explains why there exists an ethnic difference in dose, and further discusses which direction we should go forward to solve this problem. The original recommended dose was 100 mg/m2 every 3 weeks in US and European populations, while a Japanese phase I study suggested the recommended dose as 60 mg/m2 every 3 weeks. A prospective population pharmacokinetic analysis of docetaxel conducted in both the USA/Europe and Japan, indicated an absence of ethnic difference in the pharmacokinetics. Both analyses demonstrated that docetaxel clearance is related to α1-acid glycoprotein level, hepatic function, age and body surface area. The relationship was observed between increasing docetaxel dose and increased tumor response rates across the dose range of 60 to 100 mg/m2. The area under the serum concentration time curve (AUC) of docetaxel at the first cycle was significantly related to time to progression. Hematological toxicities were well correlated with the AUC of docetaxel, and severe hematological toxicities were more frequently observed in Japanese patients treated with 60 mg/m2, compared to the US/European patients treated with 75–100 mg/m2 dose. The Japanese population seems more susceptible to the toxicity of docetaxel. A docetaxel dose of 75 mg/m2 is now standard not only in global trials but also in recent Japanese trials. Although the optimal dose of docetaxel is still unclear, we need to continue to seek the appropriate dose of docetaxel depending on patient status and the goals of chemotherapy.

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“…Therefore, a low CI max indicates the inhibition of these inflammatory reactions. Recently, it has been reported [29, 30] that single nucleotide polymorphisms (SNPs) determine the individual components and/or the total white blood cell count. Furthermore, SNPs may correlate with the incidence of chemotherapy-induced neutropenia.…”

Section: Discussionmentioning

confidence: 99%

The maximum chemiluminescence intensity predicts severe neutropenia in gemcitabine-treated patients with pancreatic or biliary tract cancer

Goto

Matsuyama

Suwa

et al. 2018

Cancer Chemother Pharmacol

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An SNP in CYP39A1 is associated with severe neutropenia induced by docetaxel

Abstract: This SNP in CYP39A1 may be a useful biomarker for predicting the risk of docetaxel-induced neutropenia.

Cited by 27 publications

References 24 publications

Clarifying busulfan metabolism and drug interactions to support new therapeutic drug monitoring strategies: a comprehensive review

Clarifying busulfan metabolism and drug interactions to support new therapeutic drug monitoring strategies: a comprehensive review

Pharmacokinetics, dynamics and toxicity of docetaxel: Why the Japanese dose differs from the Western dose

The maximum chemiluminescence intensity predicts severe neutropenia in gemcitabine-treated patients with pancreatic or biliary tract cancer

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