title: Differences in adverse event profiles between everolimus and temsirolimus and the risk factors for non-infectious pneumonitis in advanced renal cell carcinoma.
abstract: BACKGROUND
  There have been few reports of the differences in safety between the mammalian target of rapamycin inhibitors, everolimus and temsirolimus. The purpose of this study is to compare the adverse event profiles of both agents and to estimate the risk factors for non-infectious pneumonitis in patients with advanced renal cell carcinoma on the basis of our real-world clinical experience.
  
  
  METHODS
  Data from 218 consecutive patients that received either everolimus or temsirolimus for advanced renal cell carcinoma at five Japanese centers were retrospectively analyzed. Chi-squared test and univariate and multivariate logistic regression analyses were performed to investigate the differences in adverse event profiles and the risk factors associated with non-infectious pneumonitis, respectively.
  
  
  RESULTS
  A total of 196 patients were evaluable. In the everolimus group compared with temsirolimus, stomatitis (56 vs 30 %, p < 0.001) and non-infectious pneumonitis (38 vs 22 %, p = 0.018) were more frequently observed, and asthenia (11 vs 23 %, p = 0.027), rash (20 vs 36 %, p = 0.018), and fatigue (33 vs 48 %, p = 0.032) occurred less frequently in all grades. On multivariate analysis, male gender (odds ratio 3.65; 95 % confidence interval 1.44-9.26, p = 0.007) and everolimus treatment (odds ratio 2.00; 95 % confidence interval 1.01-3.96, p = 0.046) were significantly associated with development of non-infectious pneumonitis.
  
  
  CONCLUSIONS
  Our findings suggest that adverse event profiles may differ between everolimus and temsirolimus and that non-infectious pneumonitis may occur more frequently in patients treated with everolimus than temsirolimus. Further investigations are needed to confirm these results.
authors.affiliation: Department of Urology, Kinki University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan, nozawa06@med.kindai.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nozawa
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ohzeki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tamada
authors.forename: Fumiya
authors.initials: F
authors.lastname: Hongo
authors.forename: Satoshi
authors.initials: S
authors.lastname: Anai
authors.forename: Kiyohide
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Tsuneharu
authors.initials: T
authors.lastname: Miki
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Nakatani
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fukasawa
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Uemura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D000068338:Everolimus / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000139:chemically induced*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D012307:Risk Factors; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C401859:temsirolimus; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus