Clinical study of neoadjuvant therapy of tyrosine kinase inhibitor in high–risk renal cell carcinoma

Abstract

Objective To investigate the safety and clinical significance in presurgical application of tyrosine kinase inhibitor (TKI) targeted therapy in high–risk renal–cell–carcinoma patients. Methods TKI targeted therapy was applied to 33 high–risk renal–cell–carcinoma patients from Jun. 2010 to Dec. 2013, 7 cases with paraneoplastic symdromes and 1 with bilateral lesions received surgical treatments. There were 6 males and 2 females in this group with average age of 50 (42–56) years. They were high–risk patients because of renal tumor and vena caval tumor thrombus in 3 cases, renal tumor and vena caval tumor thrombus and hypercalcinemia in 1 case, renal tumors with metastasis to lung and lymph nodes in 2 cases, renal tumor with metastasis to lung and bones in 1 cases, and bilateral kidney cancer in 1 case. The clinical stages included 3 cases of T3aN1M1 and T3bN0M0 respectively, and 1 case of T3bN0M1 and T3aN0M0, respectively. The primary metastasis sites were lymph nodes and lung (3 cases respectively), and another 1 in bone. 4 cases suffered from vena cava tumor thrombi with 3 staged Mayo Ⅲ and 1 Mayo Ⅳ. 7 cases with paraneoplastic syndromes were contra–indicated for surgery due to poor ECOG performance score (with score 3 in 3 cases and 2 in 4 cases). 4 cases received Sorafinib 400mg po bid and the other 4 Sunitinib 50 mg po qd, 4 weeks on and 2 weeks off, with duration of 8–12 weeks. Medical therapy ceased 6 to 16 days (median 12 days) before operation. Results Patients with neoadjuvant therapy experienced good toleration. The 7 cases with poor ECOGs improved during medical therapy. The tumor sizes in the bilateral lesions shrunk remarkably. All 7 patients received surgery: 3 radical nephrectomies, 4 nephrectomies and resections of Vena Caval tumor thrombus, and 1 bilateral lesions underwent nephron sparing surgery. Operations were successful though with mild to moderate adhesion, and the blood loss ranged from 120 to 500 ml, with averaged of 280 ml. Pathologic results were clear–cell renal carcinomas. All incisions were well–healed. 4 patients with metastasis continued TKI therapy. All patients were alive without recurrence during the follow–up of 4 to 42 mon. Conclusions Presurgical application of targeted therapy is safe and may increase the opportunity of surgery for some patients with poor general situation, also patients with bilateral lesions may benefit from it for its possibility of nephron sparing. Key words: Tyrosine kinase inhibitor targeted therapy; High–risk renal cell carcinoma; Presurgical treatment; Paraneoplastic syndrome