title: Efficacy and safety of sunitinib in the treatment of metastatic renal cell carcinoma.
abstract: BACKGROUND
  The tyrosine kinase inhibitors (TKIs) sunitinib, the first targeted agent for the first line treatment of metastatic renal cell carcinoma (RCC), targets the vascular endothelial growth factor (VEGF) pathway. The objective of this study was to investigate the efficacy and safety of sunitinib in treating metastatic clear-cell RCC and to confirm if hypertension is an effective predictive factor.
  
  
  METHODS
  A total of 36 patients with metastatic RCC were enrolled between June 2008 and December 2010. Among them 29 cases were first line therapy and 7 cases were in progression on first-line cytokine or sorafinib therapy. The pathology of all patients was confirmed predominant in clear cell type. Sunitinib mono-therapy was administered in repeated 6-week cycles of daily oral therapy for 4 weeks, followed by 2 weeks off in 34 patients; and 3 patients were administered with 37.5 mg/d continuously until disease progression or unacceptable toxicities occurred. Overall response rate and safety were evaluated. We divided patients into Group A and Group B according to the blood pressure level.
  
  
  RESULTS
  The median follow-up was 15 months (10 cycles, range 1.5 - 30.0 months (1 - 20 cycles)). Ten patients (29.4%) achieved partial responses (PR); 23 patients (67.6%) demonstrated stable disease (SD) lasting ≥ 2 cycles. Seventeen patients (50%) developed progressive disease (PD) during follow-up. The median progression-free survival (PFS) was 15 months (range 3.0 - 28.5) months. A total of 9 patients died; the overall survival has not been reached; the median survival time of the deceased patients was 13 months (range 7 - 24) months. The most common adverse events were hand-foot syndrome (77.8%), thrombocytopenia (75.0%), hypertension (61.1%) and diarrhea (46.0%). Most adverse events were reversible by treatment interruption. Twenty-two patients (61.1%) developed hypertension; and hypertension was associated with a long time to disease progression and long overall survival (P = 0.004, 0.000, respectively).
  
  
  CONCLUSIONS
  The results of this study demonstrate the efficacy and manageable adverse event profile of sunitinib as a single agent in first- or second-line therapy for patients with metastatic clear cell RCC. Further, sunitinib-associated hypertension may be a strong predictive marker for treatment efficacy in metastatic RCC.
authors: Department of Urology, Peking University First Hospital, Institute of Urology, Peking University, National Urological Cancer Center, Beijing 100034, China.
authors: Xue-Song
authors: XS
authors: Li
authors: Xiang
authors: X
authors: Wu
authors: Peng-Ju
authors: PJ
authors: Zhao
authors: Li-Hua
authors: LH
authors: Huang
authors: Yi
authors: Y
authors: Song
authors: Kan
authors: K
authors: Gong
authors: Cheng
authors: C
authors: Shen
authors: Wei
authors: W
authors: Yu
authors: Gang
authors: G
authors: Song
authors: Zheng
authors: Z
authors: Zhao
authors: Zheng
authors: Z
authors: Zhang
authors: Qian
authors: Q
authors: Zhang
authors: Gang
authors: G
authors: Wang
authors: Zhi-Song
authors: ZS
authors: He
authors: Li-Qun
authors: LQ
authors: Zhou
authors: Jie
authors: J
authors: Jin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077210:Sunitinib; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib