title: Phase II study of erlotinib in patients with locally advanced or metastatic papillary histology renal cell cancer: SWOG S0317.
abstract: OBJECTIVE
  Patients with advanced papillary renal cell cancer (pRCC) have poor survival after systemic therapy; the reported median survival time is 7 to 17 months. In this trial, we evaluated the efficacy of erlotinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor in patients with advanced pRCC, a tumor type associated with wild-type von Hippel Lindau gene.
  
  
  METHODS
  Patients with histologically confirmed, advanced, or metastatic pRCC were treated with erlotinib 150 mg orally once daily. A RECIST (Response Evaluation Criteria in Solid Tumors) response rate (RR) of > or = 20% was considered a promising outcome. Secondary end points included overall survival and 6-month probability of treatment failure.
  
  
  RESULTS
  Of 52 patients registered, 45 were evaluable. The overall RR was 11% (five of 45 patients; 95% CI, 3% to 24%), and the disease control rate was 64% (ie five partial response and 24 stable disease). The median overall survival time was 27 months (95% CI, 13 to 36 months). Probability of freedom from treatment failure at 6 months was 29% (95% CI, 17% to 42%). There was one grade 5 adverse event (AE) of pneumonitis, one grade 4 thrombosis, and nine other grade 3 AEs.
  
  
  CONCLUSIONS
  Although the RECIST RR of 11% did not exceed prespecified estimates for additional study, single-agent erlotinib yielded disease control and survival outcomes of interest with an expected toxicity profile. The design of future trials of the EGFR axis in pRCC should be based on preclinical or molecular data that define appropriate patient subgroups, new drug combinations, or potentially more active alternative schedules.
authors.affiliation: Premiere Oncology of Arizona, Scottsdale, AZ 85260, USA. mgordon@premiereoncology.com
authors.forename: Michael S
authors.initials: MS
authors.lastname: Gordon
authors.forename: Michael
authors.initials: M
authors.lastname: Hussey
authors.forename: Raymond B
authors.initials: RB
authors.lastname: Nagle
authors.forename: Primo N
authors.initials: PN
authors.lastname: Lara
authors.forename: Philip C
authors.initials: PC
authors.lastname: Mack
authors.forename: Janice
authors.initials: J
authors.lastname: Dutcher
authors.forename: Wolfram
authors.initials: W
authors.lastname: Samlowski
authors.forename: Joseph I
authors.initials: JI
authors.lastname: Clark
authors.forename: David I
authors.initials: DI
authors.lastname: Quinn
authors.forename: Chong-Xian
authors.initials: CX
authors.lastname: Pan
authors.forename: David
authors.initials: D
authors.lastname: Crawford
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D066246:ErbB Receptors / Q000032:analysis / Q000037:antagonists & inhibitors*; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D015996:Survival Rate; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000032:analysis
chemical_list: D066246:ErbB Receptors; D000069347:Erlotinib Hydrochloride; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C508053:ERBB2 protein, human; C497446:VHL protein, human