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.
ABSTRACT
Objective To evaluate the efficacy and safety of sunitinib as post-operative adjuvant therapy in patients with high-risk renal cell carcinoma (RCC).Methods A total of 60 patients with resected,histologically confirmed clear cell RCC were enrolled in this study.Patients received orally sunitinib either at a dose of 50 mg on treatment schedule (once daily for 4 weeks followed by 2 weeks off) or at a dose of 37.5 mg once daily for three 6-week cycles from 1 month after surgery.Results All the 60 patients tolerated Sunitinib treatment well and no patient discontinued treatment due to adverse events.Most adverse events were grade Ⅰ to Ⅱ.The most frequently reported adverse events were neutropenia (56.7％),thrombocytopenia (53.3％),leucopenia (48.3％),hand-foot syndrome (46.7％) and hypertension (36.7％).The most frequently reported grade 3 or 4 toxicities were thrombocytopenia (25.0％),neutropenia (15.0％),hand-foot syndrome (11.7％) and leucopenia (8.3％).The majority of adverse events occurred within the first 1-2 cycles of sunitinib treatment,and was ameliorated 1 month after 3 cycles finished.No irreversible adverse event was observed.As of April 5,2012,no recurrence occurred in patients except one death due to cerebrovascular accident unrelated to treatment,with both 6-month and 9-month disease-free survival rate of 100％.Conclusions Myelosuppression occurred less frequently in high-risk RCC patients treated with sunitinib as operative adjuvant therapy than in advanced RCC patients,with a better benefit trend.However,long-term follow-up data are needed to further confirm the efficacy of sunitinib in the adjuvant setting.