title: Analyzing the pivotal trial that compared sunitinib and IFN-α in renal cell carcinoma, using a method that assesses tumor regression and growth.
abstract: OBJECTIVE
  We applied a method that analyzes tumor response, quantifying the rates of tumor growth (g) and regression (d), using tumor measurements obtained while patients receive therapy. We used data from the phase III trial comparing sunitinib and IFN-α in metastatic renal cell carcinoma (mRCC) patients.
  
  
  METHODS
  The analysis used an equation that extracts d and g.
  
  
  RESULTS
  For sunitinib, overall survival (OS) was strongly correlated with log g (Rsq = 0.44, P < 0.0001); much less with log d (Rsq = 0.04; P = 0.0002). The median g of tumors in these patients (0.00082 per days; log g = -3.09) was about half that (P < 0.001) of tumors in patients receiving IFN-α (0.0015 per day; log g = -2.81). With IFN-α, the OS/log g correlation (Rsq = 0.14) was weaker. Values of g from measurements obtained by study investigators or central review were highly correlated (Rsq = 0.80). No advantage resulted in including data from central review in regressions. Furthermore, g can be estimated accurately four months before treatment discontinuation. Extrapolating g in a model that incorporates survival generates the hypothesis that g increased after discontinuation of sunitinib but did not accelerate.
  
  
  CONCLUSIONS
  In patients with mRCC, sunitinib reduced tumor growth rate, g, more than did IFN-α. Correlating g with OS confirms earlier analyses suggesting g may be an important clinical trial endpoint, to be explored prospectively and in individual patients.
authors.affiliation: Medical Oncology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Wilfred D
authors.initials: WD
authors.lastname: Stein
authors.forename: Julia
authors.initials: J
authors.lastname: Wilkerson
authors.forename: Sindy T
authors.initials: ST
authors.lastname: Kim
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Motzer
authors.forename: Antonio Tito
authors.initials: AT
authors.lastname: Fojo
authors.forename: Susan E
authors.initials: SE
authors.lastname: Bates
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D018572:Disease-Free Survival; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011758:Pyrroles / Q000627:therapeutic use*; D012074:Remission Induction / Q000379:methods; D000077210:Sunitinib; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D016898:Interferon-alpha; D011758:Pyrroles; D000077210:Sunitinib