d, the median PFS and OS were more than four-fold longer for patients with hypertension than for patients without hypertension [22] [23] . Rini et al. hypothesized that the susceptibility of normal blood vessels to VEGF blockade, which would lead to hypertension, is linked to the susceptibility of the tumor vessels to VEGF blockade, resulting in a more robust antiangiogenic effect in response to sunitinib treatment, and hence, enhanced clinical outcomes [22] .

Given the small number of cases without axitinib-induced hypertension, we were unable to compare the PFS and OS between groups of patients with and without hypertension; however, we suspect that the high frequency of axitinib-induced hypertension in Japanese patients is a key factor that is associated with the long PFS.

Similarly, the frequency of proteinuria (77%) in this study was higher than that reported for studies carried out in western countries (8% - 28%) [6] [10] . Proteinuria is a widely reported side effect that occurs after VEGF signaling is inhibited, and it may reflect severe glomerular damage [24] . The pathogenesis of proteinuria in patients receiving anti-VEGF therapy likely relates to multiple pathways, including post-exercise proteinuria-like syndrome [25] , the perturbation of podocyte-endothelial VEGF axis signaling [26] [27] , podocyte protein junction downregulation [28] , and subacute glomerular thrombotic microangiopathy [24] . On the other hand, no major differences were found between Asian and Caucasian people in relation to axitinib plasma pharmacokinetics during the phase I pharmacokinetic studies [29] [30] . Thus, the reasons underlying the high frequency of proteinuria among Japanese patients treated with axitinib remain unclear.

Although the differences were not significant, the median PFS tended to be longer in patients with axitinib- induced proteinuria (38.8 months) than in those without proteinuria (27.5 months). We consider that careful mo- nitoring of proteinuria and management to control proteinuria might lead to longer PFS and OS.

Hand-foot syndrome and hypothyroidism were also commonly reported AEs in this study, but they were effectively managed with axitinib dose reductions or interruptions and thyroid medications.

The limitations of this study include its retrospective nature and the small number of patients. Furthermore, the duration of the observation period was insufficient to draw definitive conclusions in relation to the prognostic issues.

5. Conclusion

Axitinib as a first-line therapy demonstrated significant efficacy in the treatment of mRCC in Japanese patients. However, the incidence rates of some AEs, including proteinuria and hypertension, were higher in Japanese patients than the patients from western countries. Thus, careful monitoring and management to control these toxicities are important to improve patients’ prognoses.

Acknowledgements

Takeshi Ueda received lecture fee from Pfizer Japan Inc.

Hirotsugu Uemura received lecture fee and research funding from Pfizer Japan Inc.

Other authors have no conflicts of interest.

Cite this paper

TakeshiNamekawa,SatoshiFukasawa,AtsushiKomaru,MasayukiKobayashi,TakayukiOhzeki,YosukeSato,JunryoRii,HirotsuguUemura,TomohikoIchikawa,TakeshiUeda, (2015) Efficacy and Safety of Axitinib as First-Line Therapy in Japanese Patients with Metastatic Renal Cell Carcinoma. Journal of Cancer Therapy,06,670-678. doi: 10.4236/jct.2015.68074

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