| Title |
Contribution of UGT1A1 genetic polymorphisms related to axitinib pharmacokinetics to safety and efficacy in patients with renal cell carcinoma
|
|---|---|
| Published in |
Medical Oncology, March 2018
|
| DOI | 10.1007/s12032-018-1113-8 |
| Pubmed ID | |
| Authors |
Ryoma Igarashi, Takamitsu Inoue, Nobuhiro Fujiyama, Norihiko Tsuchiya, Kazuyuki Numakura, Hideaki Kagaya, Mitsuru Saito, Shintaro Narita, Shigeru Satoh, Takenori Niioka, Masatomo Miura, Tomonori Habuchi |
| Abstract |
Axitinib is a potent second-line molecular-targeted agent for metastatic renal cell carcinoma (mRCC). Axitinib pharmacokinetics and its relation with genetic polymorphisms were evaluated to predict the adverse events (AEs) and efficacy of axitinib. We analyzed 46 patients with mRCC who were treated with axitinib. The plasma axitinib level was measured at 0, 2, 4, 8, and 12 h after administration (C0, C2, C4, C8, and C12; ng/mL) on day 7 of the treatment. Genetic polymorphisms related to axitinib pharmacokinetics, including SLCO1B1, SLCO1B3, SLCO2B1, ABCB1, ABCG2, CYP2C19, CYP3A5, and UGT1A1, were analyzed. Axitinib C0 and AUC0-12 in patients with UGT1A1 poor metabolisers (*6/*6, *6/*28, and *28/*28; n = 10) were significantly higher than those in patients with UGT1A1 extensive metabolisers (*1/*1, *1/*6,*1/*28, and *27/*28; n = 36) (23.6 vs. 7.8 ng/mL, p = 0.030, and 441.3 vs. 217.1 ng h/mL, p = 0.007). The cutoff levels of C0 to predict ≥ G2 hypothyroidism and ≥ G2 anorexia were 6.6 and 7.1 ng/mL, respectively (p = 0.005 and p = 0.035). The overall survival (OS) in patients with C0 > 5 ng/mL was significantly better than that in patients with C0 < 5 ng/mL (p = 0.022). Genetic polymorphisms in UGT1A1 were significantly associated with the plasma axitinib level. The plasma axitinib level was significantly associated with the frequency of AEs and OS in patients with mRCC. No direct relationship was observed between UGT1A1 genotypes and the frequency of AEs or OS. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 3 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 31 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 31 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 4 | 13% |
| Other | 2 | 6% |
| Student > Doctoral Student | 2 | 6% |
| Student > Bachelor | 2 | 6% |
| Lecturer | 1 | 3% |
| Other | 3 | 10% |
| Unknown | 17 | 55% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 3 | 10% |
| Medicine and Dentistry | 3 | 10% |
| Nursing and Health Professions | 2 | 6% |
| Unspecified | 1 | 3% |
| Psychology | 1 | 3% |
| Other | 3 | 10% |
| Unknown | 18 | 58% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. 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 15 March 2018.
All research outputs
#14,378,457
of 23,026,672 outputs
Outputs from Medical Oncology
#561
of 1,301 outputs
Outputs of similar age
#188,959
of 332,340 outputs
Outputs of similar age from Medical Oncology
#10
of 27 outputs
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