title: Efficacy of sunitinib re-exposure after failure of an mTOR inhibitor in patients with metastatic RCC.
abstract: BACKGROUND
  The sequential use of tyrosine kinase inhibitors (TKI) followed by mTOR inhibitors (mTORi) has been recently established for the systemic treatment of metastatic renal cell carcinoma (mRCC). However, subsequent treatment in mTORi-refractory disease remains undetermined. We analyzed the efficacy of sunitinib re-challenge after failure of an mTORi at 2 German centers.
  
  
  METHODS
  Thirteen patients who failed both sunitinib and an mTORi were analyzed, and all patients were re-exposed to sunitinib. Tumor assessment was performed every 2nd cycle of sunitinib or every 3 months. Tumor response was assessed according to RECIST criteria.
  
  
  RESULTS
  Initial treatment with sunitinib was associated with a median progression free survival (PFS) of 21 months. Objective response consisted of 2 (15%) complete remissions and 7 (54%) partial remissions (PR) as best response. At the time of re-exposure, 12 of 13 (92%) patients again showed clinical benefit which was associated with a median PFS of 6.9 months and consisted of 2 (15%) PR and 10 (77%) disease stabilizations.
  
  
  CONCLUSIONS
  In sunitinib-responsive patients, re-challenge with sunitinib has been successfully introduced after mTORi-refractory disease, underscoring the at least partially transient nature of TKI resistance in mRCC.
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Medical School Hannover, Germany. Gruenwald.Viktor@MH-Hannover.de
authors.forename: Viktor
authors.initials: V
authors.lastname: Grünwald
authors.forename: Steffen
authors.initials: S
authors.lastname: Weikert
authors.forename: Christoph
authors.initials: C
authors.lastname: Seidel
authors.forename: Jonas
authors.initials: J
authors.lastname: Busch
authors.forename: Antje
authors.initials: A
authors.lastname: Johannsen
authors.forename: Martin
authors.initials: M
authors.lastname: Fenner
authors.forename: Christoph
authors.initials: C
authors.lastname: Reuter
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.forename: Manfred
authors.initials: M
authors.lastname: Johannsen
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary*; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use*; D000077210:Sunitinib; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D000077210:Sunitinib