title: Sunitinib treatment for patients with clear-cell metastatic renal cell carcinoma: clinical outcomes and plasma angiogenesis markers.
abstract: BACKGROUND
  Sunitinib is a protein tyrosine kinase-inhibitor targeting VEGFR, c-kit and PDGFR. It has been approved for the treatment of metastatic renal-cell carcinoma and gastrointestinal stromal tumors. Although it has been shown to prolong disease-free and overall survival in renal-cell carcinoma patients, only 70% of the treated population receive a clinical benefit (CB) from the treatment. Markers that could predict clinical benefit to sunitinib would be an important aid in monitoring and following their treatment. We assessed the outcome and plasma proangiogenic factors in patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib in our institution.
  
  
  METHODS
  We have treated 42 patients with metastatic clear-cell renal carcinoma with sunitinib. Plasma concentrations of VEGF-A, sVEGFR2 and PDGF were determined by ELISA.
  
  
  RESULTS
  At the time of analysis 39 patients were evaluable for response and 30 patients had obtained a clinical benefit (CB). Median progression-free survival was 268 days (8.93 months) and median overall survival was 487 days (16.23 months). Interestingly, disease stabilization or objective response resulted in comparable overall survival. Most treatment-related adverse events were of mild-to-moderate intensity with one treatment-related death. Plasma sVEGFR2 and PDGF levels had no predictive value. Fold-increase in plasma VEGF was significantly lower in patients that obtained a CB as compared to patients that progressed after two cycles of treatment. Plasma VEGF did not increase in patients with initial CB at the time of progression.
  
  
  CONCLUSIONS
  Sunitinib showed substantial activity in mRCC. Disease stabilization or objective response resulted in comparable overall survival and both outcomes should be considered positive. Fold-increase in plasma VEGF predicts for CB and could be a candidate marker. Progression after initial CB is not associated with elevated plasma VEGF, implying a different mechanism of resistance.
authors.affiliation: 3rd Department of Medical Oncology, Theagenion Cancer Hospital, Al Simeonidi str. 2, 54007, Thessaloniki, Greece. loukas.kontovinis@gmail.com
authors.forename: Loukas F
authors.initials: LF
authors.lastname: Kontovinis
authors.forename: Konstantinos T
authors.initials: KT
authors.lastname: Papazisis
authors.forename: Panagiota
authors.initials: P
authors.lastname: Touplikioti
authors.forename: Charalambos
authors.initials: C
authors.lastname: Andreadis
authors.forename: Despoina
authors.initials: D
authors.lastname: Mouratidou
authors.forename: Alexandros H
authors.initials: AH
authors.lastname: Kortsaris
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000097:blood; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000097:blood; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis; D011379:Prognosis; D011758:Pyrroles / Q000627:therapeutic use*; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D000077210:Sunitinib; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007211:Indoles; D010982:Platelet-Derived Growth Factor; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; C075278:platelet-derived growth factor A; D017479:Receptors, Platelet-Derived Growth Factor; D040262:Receptors, Vascular Endothelial Growth Factor; D040301:Vascular Endothelial Growth Factor Receptor-2; D000077210:Sunitinib