title: Continuing a cancer treatment despite tumor growth may be valuable: sunitinib in renal cell carcinoma as example.
abstract: BACKGROUND
  The US FDA and the EMA have approved seven agents for the treatment of renal cell carcinoma, primarily based on differences in progression-free survival (PFS). Because PFS is an arbitrary endpoint we hypothesized that an analysis would demonstrate the growth rate of tumors remained constant at the time of RECIST-defined disease progression.
  
  
  METHODS
  We previously estimated the growth (g) and regression (d) rates and the stability of g using data from the Phase III trial comparing sunitinib and interferon.
  
  
  RESULTS
  Sufficient data were available and rate constants statistically valid in 321 of 374 patients randomized to sunitinib. Median d was 0•0052 days(-1); in 53 patients no tumor growth was recorded. Median g was 0•00082 days(-1) and was stable for a median of 275 days on therapy, remaining stable beyond 300, 600 and 900 days in 122, 65 and 27 patients, respectively. A possible increase in g while receiving sunitinib could be discerned in only 18 of 321 patients. Given a median g of 0•00082 days(-1) the estimated median time to a second progression were sunitinib continued past RECIST-defined progression was 7.3 months. At 100, 200, and 300 days after starting therapy, an estimated 47%, 27%, and 13% of tumor remains sunitinib sensitive and could explain a RECIST-defined response to a new TKI.
  
  
  CONCLUSIONS
  Prolonged stability of g with sunitinib suggests continued sunitinib beyond RECIST-defined progression may provide a beneficial outcome. Randomized trials in patients whose disease has "progressed" on sunitinib are needed to test this hypothesis.
authors.affiliation: Medical Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland, United States of America.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Burotto
authors.affiliation: Medical Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland, United States of America.
authors.forename: Julia
authors.initials: J
authors.lastname: Wilkerson
authors.affiliation: Medical Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland, United States of America; Hebrew University, Jerusalem, Israel.
authors.forename: Wilfred
authors.initials: W
authors.lastname: Stein
authors.affiliation: Memorial Sloan Kettering Cancer Institute, New York, New York, United States of America.
authors.forename: Robert
authors.initials: R
authors.lastname: Motzer
authors.affiliation: Medical Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland, United States of America.
authors.forename: Susan
authors.initials: S
authors.lastname: Bates
authors.affiliation: Medical Oncology Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland, United States of America.
authors.forename: Tito
authors.initials: T
authors.lastname: Fojo
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D049109:Cell Proliferation / Q000187:drug effects; D018572:Disease-Free Survival; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007680:Kidney Neoplasms; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077210:Sunitinib; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib