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Severe toxicity induced by accumulation of active sunitinib metabolite in a Japanese patient with renal cell carcinoma: a case report

Overview of attention for article published in Journal of Medical Case Reports, February 2017
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Title
Severe toxicity induced by accumulation of active sunitinib metabolite in a Japanese patient with renal cell carcinoma: a case report
Published in
Journal of Medical Case Reports, February 2017
DOI 10.1186/s13256-016-1185-z
Pubmed ID
Authors

Shinya Takasaki, Masafumi Kikuchi, Yoshihide Kawasaki, Akihiro Ito, Yoichi Arai, Hiroaki Yamaguchi, Nariyasu Mano

Abstract

Sunitinib is a multi-targeted tyrosine kinase inhibitor that is approved for treatment of renal cell carcinoma as an oral anticancer drug. Therapeutic drug monitoring of total sunitinib (sunitinib and N-desethyl sunitinib) is used in our hospital to improve therapeutic efficacy, while preventing adverse effects. Here, we report the first case of a patient with metastatic renal cell carcinoma undergoing hemodialysis and presenting severe adverse events induced by the accumulation of N-desethyl sunitinib. A 60-year-old Japanese man was diagnosed with metastatic renal cell carcinoma requiring hemodialysis. On day 26 of the first cycle of sunitinib therapy, our patient presented grade 3 thrombocytopenia and leukopenia, which required interruption of therapy although the plasma levels of total sunitinib in the patient were less than the effective concentration of 50 ng/mL. The elimination half-life of sunitinib was normal at 50.8 hours, but that of N-desethyl sunitinib was an extended 211.4 hours. Moreover, the N-desethyl sunitinib/sunitinib trough level ratio was higher than 1.0. We attribute our patient's severe adverse events to the excessive accumulation of N-desethyl sunitinib owing to its delayed excretion. Although the reason for the delayed excretion of N-desethyl sunitinib in this patient was unknown, it may have been caused by genetic polymorphisms related to the pharmacokinetics of sunitinib rather than the hemodialysis. In this case, the patient was homozygous for the ABCG2 421C allele, but was capable of potentially harboring polymorphisms in other genes, such as ABCB1, an efflux pump of sunitinib. In addition, even though there is no clear evidence, urinary excretion of the metabolic products of N-desethyl sunitinib could be inhibited by the interaction of transporters such as the organic ion transporter. The monitoring of not only total sunitinib concentration but also N-desethyl sunitinib concentration and their elimination half-lives during sunitinib therapy is recommended to avoid critical adverse events.

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Mendeley readers

The data shown below were compiled from readership statistics for 24 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 24 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 3 13%
Student > Master 3 13%
Researcher 2 8%
Lecturer 2 8%
Student > Bachelor 1 4%
Other 6 25%
Unknown 7 29%
Readers by discipline Count As %
Medicine and Dentistry 7 29%
Pharmacology, Toxicology and Pharmaceutical Science 5 21%
Unspecified 1 4%
Psychology 1 4%
Nursing and Health Professions 1 4%
Other 0 0%
Unknown 9 38%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 09 February 2017.
All research outputs
#9,071,179
of 11,330,364 outputs
Outputs from Journal of Medical Case Reports
#944
of 1,684 outputs
Outputs of similar age
#227,253
of 320,426 outputs
Outputs of similar age from Journal of Medical Case Reports
#42
of 100 outputs
Altmetric has tracked 11,330,364 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,684 research outputs from this source. They receive a mean Attention Score of 3.4. This one is in the 16th percentile – i.e., 16% of its peers scored the same or lower than it.
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