title: Axitinib for preoperative downstaging of renal cell carcinoma with sarcomatoid differentiation and direct invasion of the duodenum and inferior vena cava: a case report.
abstract: BACKGROUND
  Renal cell carcinoma (RCC) with sarcomatoid differentiation is invasive, refractory to treatment, and has a higher mortality. Therefore, systemic therapy is still challenging, and the curative resection of localized or locally advanced RCC with sarcomatoid differentiation is very important. Axitinib is a potent and selective second-generation vascular endothelial growth factor receptor tyrosine kinase inhibitor with improved safety and tolerability. Axitinib is generally recommended as second-line therapy for advanced RCC because the phase III axitinib versus sorafenib in advanced RCC (AXIS) trial demonstrated that it achieved longer progression-free survival than sorafenib in patients with metastatic RCC after failure of an approved first-line regimen.
  
  
  METHODS
  We present a 73-year-old man who had a large (13 cm in diameter) right RCC with sarcomatoid differentiation that directly invaded the duodenum and inferior vena cava. The patient presented with gastrointestinal bleeding, was unable to eat solid food, and had become emaciated. Thus, his classification was poor risk with anemia, hypercalcemia, and poor performance status, according to the Memorial Sloan-Kettering Cancer Center criteria. He seemed unlikely to survive if radical nephrectomy, cavotomy with thrombectomy, and pancreatoduodenectomy were performed. To reduce the tumor burden and potential operative complications, we administered axitinib as first-line neoadjuvant therapy.
  
  
  RESULTS
  Six weeks of treatment reduced the tumor burden without causing severe toxicities. Subsequently, radical right nephrectomy, cavotomy with thrombectomy, and pancreatoduodenectomy were performed successfully. The pathological treatment effect of axitinib was grade 2 (two-thirds necrosis). The resected tumor showed a heterogeneous reaction for phosphorylated Akt (Ser-473) by Western blotting and immunohistochemistry, indicating that parts of the tumor were sensitive to axitinib and other parts were not.
  
  
  CONCLUSIONS
  Axitinib might be promising as preoperative or neoadjuvant therapy for locally advanced RCC (>cT3b or >cTanyN1).
authors.affiliation: Department of Urology, Dokkyo Medical University, Mibu, Tochigi, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Yuki
authors.affiliation: Department of Urology, Dokkyo Medical University, Mibu, Tochigi, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Kamai
authors.affiliation: Department of Gastroenterological Surgery, Dokkyo Medical University, Mibu, Tochigi, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kubota
authors.affiliation: Department of Urology, Dokkyo Medical University, Mibu, Tochigi, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Abe
authors.affiliation: Department of Urology, Dokkyo Medical University, Mibu, Tochigi, Japan.
authors.forename: Daisaku
authors.initials: D
authors.lastname: Nishihara
authors.affiliation: Department of Urology, Dokkyo Medical University, Mibu, Tochigi, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Mizuno
authors.affiliation: Department of Urology, Dokkyo Medical University, Mibu, Tochigi, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Masuda
authors.affiliation: Department of Urology, Dokkyo Medical University, Mibu, Tochigi, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Betsunoh
authors.affiliation: Department of Urology, Dokkyo Medical University, Mibu, Tochigi, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yashi
authors.affiliation: Department of Urology, Dokkyo Medical University, Mibu, Tochigi, Japan.
authors.forename: Yoshitatsu
authors.initials: Y
authors.lastname: Fukabori
authors.affiliation: Department of Urology, Dokkyo Medical University, Mibu, Tochigi, Japan.
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Yoshida
keywords: axitinib; phosphorylated Akt; renal cell carcinoma; sarcomatoid differentiation; tyrosine kinase inhibitors