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Axitinib for preoperative downstaging of renal cell carcinoma with sarcomatoid differentiation and direct invasion of the duodenum and inferior vena cava: a case report

Authors Yuki H, Kamai T, Kubota K, Abe H, Nishihara D, Mizuno T, Masuda A, Betsunoh H, Yashi M, Fukabori Y, Yoshida K

Received 22 November 2013

Accepted for publication 3 January 2014

Published 15 February 2014 Volume 2014:7 Pages 289—295


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 6

Hideo Yuki,1,* Takao Kamai,1,* Keiichi Kubota,2 Hideyuki Abe,1 Daisaku Nishihara,1 Tomoya Mizuno,1 Akinori Masuda,1 Hironori Betsunoh,1 Masahiro Yashi,1 Yoshitatsu Fukabori,1 Ken-Ichiro Yoshida1

1Department of Urology, 2Department of Gastroenterological Surgery, Dokkyo Medical University, Mibu, Tochigi, Japan

*These authors contributed equally to this manuscript

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.
Conclusion: Axitinib might be promising as preoperative or neoadjuvant therapy for locally advanced RCC (>cT3b or >cTanyN1).

Keywords: renal cell carcinoma, sarcomatoid differentiation, axitinib, tyrosine kinase inhibitors, phosphorylated Akt

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