Clinical factors associated with outcome in patients with metastatic clear-cell renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy

Cancer. 2007 Aug 1;110(3):543-50. doi: 10.1002/cncr.22827.


Background: Therapy targeted against the vascular endothelial growth factor (VEGF) pathway is a standard of care for patients with metastatic renal cell carcinoma (RCC). The identification of patients who are more likely to benefit from these agents is warranted.

Methods: In total, 120 patients with metastatic clear-cell RCC received bevacizumab, sorafenib, sunitinib, or axitinib on 1 of 9 prospective clinical trials at the Cleveland Clinic. Clinical features associated with outcome were identified by univariate analysis; then, a stepwise modeling approach based on Cox proportional hazards regression was used to identify independent prognostic factors and to form a model for progression-free survival (PFS). A bootstrap algorithm was used to provide internal validation.

Results: The overall median PFS was 13.8 months, and the objective response according to the Response Criteria in Solid Tumors was 34%. Multivariate analysis identified time from diagnosis to current treatment <2 years; baseline platelet and neutrophil counts >300 K/microL and >4.5 K/microL, respectively; baseline corrected serum calcium <8.5 mg/dL or >10 mg/dL; and initial Eastern Cooperative Oncology Group performance status >0 as independent, adverse prognostic factors (PF) for PFS. Three prognostic subgroups were formed based on the number of adverse prognostic factors present. The median PFS in patients with 0 or 1 adverse prognostic factor was 20.1 months compared with 13 months in patients with 2 adverse prognostic factors and 3.9 months in patients with >2 adverse prognostic factors.

Conclusions: Five independent prognostic factors for predicting PFS were identified and were used to categorize patients with metastatic RCC who received VEGF-targeted therapies into 3 risk groups. These prognostic factors can be incorporated into patient care and clinical trials that use such novel, VEGF-targeted agents.

MeSH terms

  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Axitinib
  • Benzenesulfonates / administration & dosage
  • Bevacizumab
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Female
  • Humans
  • Imidazoles / administration & dosage
  • Indazoles / administration & dosage
  • Indoles / administration & dosage
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Neovascularization, Pathologic
  • Niacinamide / analogs & derivatives
  • Phenylurea Compounds
  • Prognosis
  • Prospective Studies
  • Pyridines / administration & dosage
  • Pyrroles / administration & dosage
  • Randomized Controlled Trials as Topic
  • Sorafenib
  • Sunitinib
  • Survival Rate
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / immunology
  • Vascular Endothelial Growth Factor A / metabolism


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Benzenesulfonates
  • Imidazoles
  • Indazoles
  • Indoles
  • Phenylurea Compounds
  • Pyridines
  • Pyrroles
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Niacinamide
  • Bevacizumab
  • Sorafenib
  • Axitinib
  • Sunitinib