title: Sequential mTOR inhibitor treatment with temsirolimus in metastatic renal cell carcinoma following failure of VEGF receptor tyrosine kinase inhibitors.
abstract: OBJECTIVE
  Agents targeting the mammalian target of rapamycin (mTOR) pathway, e. g. everolimus, can provide clinical benefit in pretreated patients with metastatic renal cell carcinoma (mRCC), but data from randomized trials on the sequential use of temsirolimus are lacking. We retrospectively studied the efficacy and safety of temsirolimus therapy following failure of rTKI therapy.
  
  
  METHODS
  Twenty-nine patients treated with temsirolimus (25 mg/week) following progression on rTKI therapy were studied at four institutions. All patients had failed at least one prior rTKI therapy (sunitinib, n = 6; sorafenib, n = 1; both, n = 22). Over 80% had two or more prior therapies. Data on efficacy (response assessment, progression-free survival [PFS], overall survival [OS]) and safety (NCI-CTC) were analyzed.
  
  
  RESULTS
  Adverse events occurred in 90% of patients with the majority being grade 1 (n = 4, 14%) or grade 2 (n = 12, 41%). Most grade 3/4 toxicities (n = 10, 34%) were manageable and included anemia (n = 4, 14%), leukopenia/neutropenia (n = 2, 7%), hyperglycemia (n = 1, 3%), acidosis/alkalosis (n = 2, 7%), and infection (n = 1, 3%). One patient discontinued temsirolimus for grade 3 pneumonitis. Median (range) PFS and OS were 5.1 months (1-10.4) and 18.0 months (12.6-23.3), respectively. Best response included partial response (n = 1) and stable disease (n = 15) for a disease control rate of 55%, and disease progression of 45% (n = 13).
  
  
  CONCLUSIONS
  Temsirolimus after rTKI failure appears to provide promising safety and efficacy comparable to other treatment options in pretreated patients with mRCC.
authors.affiliation: Department of Urology, Charité-University Medicine Berlin, Charitéplatz 1, 10117, Berlin, Germany. steffen.weikert@charite.de
authors.forename: Steffen
authors.initials: S
authors.lastname: Weikert
authors.forename: Carsten
authors.initials: C
authors.lastname: Kempkensteffen
authors.forename: Jonas
authors.initials: J
authors.lastname: Busch
authors.forename: Manfred
authors.initials: M
authors.lastname: Johannsen
authors.forename: Viktor
authors.initials: V
authors.lastname: Grünwald
authors.forename: Kaja
authors.initials: K
authors.lastname: Zimmermann
authors.forename: Anne
authors.initials: A
authors.lastname: Flörcken
authors.forename: Jörg
authors.initials: J
authors.lastname: Westermann
authors.forename: Lisa
authors.initials: L
authors.lastname: Weinkauf
authors.forename: Kurt
authors.initials: K
authors.lastname: Miller
authors.forename: Ulrich
authors.initials: U
authors.lastname: Keilholz
mesh_terms: D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000627:therapeutic use; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D012189:Retrospective Studies; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077157:Sorafenib; D000077210:Sunitinib; D015996:Survival Rate; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D007211:Indoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D009536:Niacinamide; C401859:temsirolimus; D000077157:Sorafenib; C546842:MTOR protein, human; D011505:Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D058570:TOR Serine-Threonine Kinases; D000077210:Sunitinib; D020123:Sirolimus