Presurgical therapy with axitinib for advanced renal cell carcinoma: a case report
© Koie et al.; licensee BioMed Central Ltd. 2013
Received: 30 July 2013
Accepted: 21 November 2013
Published: 24 November 2013
Targeted therapy with tyrosine kinase inhibitors has been shown to reduce tumor volumes and prolong the survival of patients with metastatic renal cell carcinoma. Tyrosine kinase inhibitors, particularly sunitinib, have recently been used in neoadjuvant and presurgical settings. Axitinib is a promising second-line therapy option for advanced or metastatic renal cell carcinoma. Herein, we report a patient with advanced renal cell carcinoma who received presurgical treatment with axitinib.
A 73-year-old man was transported by ambulance to a community hospital with chief complaints of high fever and a gait disorder. Computed tomography screening revealed a hypervascular tumor (size, 9 × 8.5 cm) in the lower pole of the left kidney. Upon admission to our hospital, his general condition was poor and his performance status was judged as 3, based on the Eastern Cooperative Oncology Group performance status criteria. After biopsy for the renal tumor, he received 5 mg of axitinib twice daily for 3 months. No serious adverse events were reported during this treatment. The tumor diameter shrank by 56%. Left radical nephrectomy was performed, and there were no intraoperative or postoperative complications. Pathological examination indicated a pT3aN0M0, Furman grade 3, clear cell renal cell carcinoma with necrosis, hyaline degeneration, and hemosiderosis. The patient was asymptomatic and disease-free at 1 year post-diagnosis.
This case study demonstrate that presurgical therapy with axitinib is feasible and might have several potential advantages for patients with advanced renal cell carcinoma.
KeywordsClear cell carcinoma Axitinib Presurgical therapy
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 . 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 . In Japanese patients with metastatic RCC, adverse events with sunitinib was severer than the Caucasian population . Additionally, this agent has shown anti-tumor activity and has an acceptable safety profile . 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 . Recent reports have cited complications such as poor wound healing and hemorrhage . Chapin reported that presurgical targeted therapy remained a significant predictor of wound complications in a multivariate analysis (odds ratio, 4.14; P = 0.03) . 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 .
Axitinib is a potent and selective second-generation inhibitor of vascular endothelial growth factor receptor-1, 2, and 3 . 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 . Although axitinib was less effective for patients with poor PS , 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.
Renal cell carcinoma
Tyrosine kinase inhibitor.
- Motzer RJ, Huston TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST, Chen I, Bycott PW, Baum CM, Figlin RA: Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Eng J Med. 2007, 356: 115-124. 10.1056/NEJMoa065044.View ArticleGoogle Scholar
- Amin C, Wallen E, Pruthi RS, Calvo BF, Godley PA, Rathmell WK: Preoperative tyrosine kinase inhibition as an adjunct to debulking nephrectomy. Urology. 2008, 72: 864-868. 10.1016/j.urology.2008.01.088.PubMedView ArticleGoogle Scholar
- Kondo T, Hashimoto Y, Kobayashi H, Iizuka J, Nishikawa T, Nakano M, Tanabe K: Presurgical targeted therapy with tyrosine kinase inhibitors for advanced renal cell carcinoma: clinical results and histopathological therapeutic effects. Jpn J Clin Oncol. 2010, 40: 1173-1179. 10.1093/jjco/hyq150.PubMedView ArticleGoogle Scholar
- Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, Michaelson MD, Gorbunova VA, Gore ME, Rusakov IG, Negrier S, Ou YC, Castellano D, Lim HY, Uemura H, Tarazi J, Cella D, Chen C, Rosbrook B, Kim S, Motzer RJ: Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011, 378: 1931-1939. 10.1016/S0140-6736(11)61613-9.PubMedView ArticleGoogle Scholar
- Kawashima A, Tsujimura A, Takayama H, Arai Y, Nin M, Tanigawa G, Yasunaga Y, Mukai M, Uemura M, Nakai Y, Nishimura K, Nonomura N, Osaka Renal Cell Carcinoma Clinical Study Collaboration: Importance of continuing therapy and maintaining one-month relative dose intensity in sunitinib therapy for metastatic renal cell carcinoma. Med Oncol. 2012, 29: 3298-3305. 10.1007/s12032-012-0236-6.PubMedView ArticleGoogle Scholar
- Fruehauf J, Lutzky J, McDermott D, Brown CK, Meric JB, Rosbrook B, Shalinsky DR, Liau KF, Niethammer AG, Kim S, Rixe O: Multicenter, phase II study of axitinib, a selective second-generation inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, in patients with metastatic melanoma. Clin Cancer Res. 2011, 17: 7462-7469. 10.1158/1078-0432.CCR-11-0534.PubMedView ArticleGoogle Scholar
- Sobin LH: TNM Classification of Malignant Tumors. 2002, New York: Wiley-LissGoogle Scholar
- Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Freeman S, Schwartz B, Shan M, Simantov R, Bukowski RM, TARGET Study Group: Sorafenib in advanced clear-cell renal-cell carcinoma. N Eng J Med. 2007, 356: 125-134. 10.1056/NEJMoa060655.View ArticleGoogle Scholar
- Motzer RJ, Huston TE, Tomezak P, Michaelson MD, Bukowski RM, Oudard S, Negrier S, Szczylik C, Pili R, Bjarnason GA, Garcia-del-Muro X, Sosman JA, Solska E, Wilding G, Thompson JA, Kim ST, Chen I, Huang X, Figlin RA: Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009, 27: 3584-3590. 10.1200/JCO.2008.20.1293.PubMedPubMed CentralView ArticleGoogle Scholar
- Thomas AA, Rini BI, Stephenson AJ, Garcia JA, Fergany A, Krishnamurthi V, Novick AC, Gill IS, Klein EA, Zhou M, Campbell AC: Surgical resection of renal cell carcinoma after targeted therapy. J Urol. 2009, 182: 881-886. 10.1016/j.juro.2009.05.014.PubMedView ArticleGoogle Scholar
- Ficarra V, Novara G: Neoadjuvant targeted therapies in renal cell carcinoma. Nat Rev Urol. 2010, 7: 63-64. 10.1038/nrurol.2010.2.PubMedView ArticleGoogle Scholar
- Harshman LC, Yu RJ, Allen GI, Srinivas S, Gill HS, Chung BI: Surgical outcomes and complications associated with presurgical tyrosine kinase inhibition for advanced renal cell carcinoma (RCC). Urol Oncol. 2013, 31: 379-385. 10.1016/j.urolonc.2011.01.005.PubMedView ArticleGoogle Scholar
- Chapin BF, Delacroix SE, Culp SH, Nogueras Gonzalez GM, Tannir NM, Jonasch E, Tamboli P, Wood CG: Safety of presurgical targeted therapy in the setting of metastatic renal cell carcinoma. Eur Urol. 2011, 60: 964-971. 10.1016/j.eururo.2011.05.032.PubMedPubMed CentralView ArticleGoogle Scholar
- Jonasch E, Wood CG, Matin SF, Tu SM, Pagliaro LC, Corn PG, Aparicio A, Tamboli P, Millikan RE, Wang X, Araujo JC, Arap W, Tannir N: Phase II presurgical feasibility study of bevacizumab in untreated patients with metastatic renal cell carcinoma. J Clin Oncol. 2009, 27: 4076-4081. 10.1200/JCO.2008.21.3660.PubMedPubMed CentralView ArticleGoogle Scholar
- Goldstein R, Pickering L, Larkin J: Does axitinib (AG-01376) have a future role in metastatic renal cell carcinoma and other malignancies?. Expert Rev Anticancer Ther. 2010, 10: 1545-1557. 10.1586/era.10.134.PubMedView ArticleGoogle Scholar
- Ueda T, Uemura H, Tomita Y, Tsukamoto T, Kanayama H, Shinohara N, Tarazi J, Chen C, Kim S, Ozono S, Naito S, Akaza H: Efficacy and safety of axitinib versus sorafenib in metastatic renal cell carcinoma: subgroup analysis of Japanese patients from the global randomized phase 3 AXIS trial. Jpn J Clin Oncol. 2013, 43: 616-628. 10.1093/jjco/hyt054.PubMedPubMed CentralView ArticleGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.