Presurgical therapy with axitinib for advanced renal cell carcinoma: a case report

Targeted therapy with tyrosine kinase inhibitors (TKIs) has been shown to reduce primary or metastatic tumor volumes and prolong the survival of patients with metastatic renal cell carcinoma (RCC) [1, 2]. TKIs, particularly sunitinib, have recently been used in neoadjuvant or presurgical settings to facilitate surgery by reducing tumor sizes [2, 3]. The potential benefits of neoadjuvant or presurgical therapy include local tumor downstaging, elimination of micrometastatic disease, and diminution of postoperative metastatic progression.

However, targeted therapy with TKIs has elicited some concerns regarding complications. The commonly recorded grade 3/4 clinical toxicities associated with sunitinib were gastrointestinal disorders including diarrhea or anorexia, and hematotoxicity including neutropenia or thrombocytopenia [1]. Targeted therapy regimens should be less toxic to prevent any treatment-related delays between neoadjuvant therapy and surgery and to achieve better oncologic outcomes in a neoadjuvant setting.

Axitinib is a promising second-line therapy option for advanced or metastatic RCC [4]. In Japanese patients with metastatic RCC, adverse events with sunitinib was severer than the Caucasian population [5]. Additionally, this agent has shown anti-tumor activity and has an acceptable safety profile [6]. We designed a phase II single-arm trial to evaluate safety and effectiveness of presurgical treatment of advanced RCC with axitinib. This patient was enrolled this trial. Herein, we report a patient with advanced RCC who received presurgical treatment with axitinib. The patient was informed about the treatment protocol and provided written informed consent. The study protocol and informed consent documents were reviewed and approved by the Hirosaki University Institutional Review Board.

To the best of our knowledge, this is the first reported case of presurgical axitinib therapy in a patient with RCC.

Targeted molecular therapies such as sunitinib have changed the management of advanced or metastatic RCC. TKIs have significantly improved progression-free survival, and sunitinib, in particular, achieved a median overall survival of >2 years in advanced RCC patients [8, 9]. Therefore, neoadjuvant or presurgical treatments have been suggested as treatment options for patients with advanced or unresectable RCC. Several studies suggested that targeted therapies in the neoadjuvant setting were safe, well tolerated, and did not increase surgical morbidity or perioperative complications in selected patients [2, 3, 10]. However, these findings have been limited to small, uncontrolled, single-institution studies.

Potential disadvantages of presurgical or neoadjuvant targeted therapy include the lack of optimal surgical timing after systemic therapy and the risk of increased surgical morbidity [11]. Recent reports have cited complications such as poor wound healing and hemorrhage [12]. Chapin reported that presurgical targeted therapy remained a significant predictor of wound complications in a multivariate analysis (odds ratio, 4.14; P = 0.03) [13]. In a prospective study, the incidence of delayed superficial wound healing was higher in patients who received preoperative bevacizumab than in a historic matched cohort of 101 patients who underwent upfront surgery [14].

Axitinib is a potent and selective second-generation inhibitor of vascular endothelial growth factor receptor-1, 2, and 3 [15]. Axitinib has shown anti-tumor activity as a single agent with an acceptable safety profile in several solid tumors including previously treated metastatic RCC [4, 6]. Adverse events observed in Japanese patients as well as in the overall axitinib-treated population, included diarrhea, hypertension, and fatigue [16]. Although axitinib was less effective for patients with poor PS [4], axitinib was generally well tolerated and had an acceptable safety profile in Japanese patients with metastatic RCC. Therefore, axitinib was administered for advanced RCC in this case.

In conclusion, this case study indicates that presurgical targeted therapy with axitinib might have several potential advantages for patients with advanced RCC. However, the indications and clinical benefits of neoadjuvant or presurgical axitinib therapy remain to be determined. It will thus be necessary to investigate many cases in a large clinical study.

Written informed consent was obtained from the patient for the publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.