title: Safety profile and treatment response of everolimus in different solid tumors: an observational study.
abstract: OBJECTIVE
  Only few efforts have been taken to investigate the potential existence of disease-specific differences in the safety profile of everolimus. We analyze here the correlation between different patient and tumor characteristics on the safety profile of this molecule. Information on treatment response is also provided.
  
  
  METHODS
  Consecutive patients with metastatic renal cell carcinoma (mRCC), pancreatic neuroendocrine tumors (pNET) or biliary tract cancer were included in this retrospective study. All patients received everolimus 10 mg/day or 5 mg/day. Clinical assessments were performed every 3 weeks.
  
  
  RESULTS
  In total, 98 patients were enrolled: 51 with mRCC, 25 with pNET and 22 with biliary tract cancer. The incidence of toxicities (any grade) was 76% with mRCC, 64% with pNET and 95% with biliary tract cancer. Patients with biliary tract cancer also presented a higher frequency of severe toxicities: 64 versus 18% with mRCC and 32% with pNET. Multivariate analysis disclosed that biliary tract cancer (odds ratio [OR]: 23.8; 95% CI: 6.0-117.8; p < 0.0001) is a predictive factor for the development of toxicities during everolimus treatment. No correlations between liver metastasis and toxicities were identified. Disease control rate (DCR) was 45% in mRCC patients, 96% in pNET and 50% for biliary tract cancer patients. pNET tumors were associated with a higher DCR than the mRCC and biliary tract cancer (OR vs mRCC: 66.7; 95% CI: 6.2-276.5; p = 0.004; OR vs biliary tract cancer: 2.6; 95% CI: 0.5-14.2; p = 0.025).
  
  
  CONCLUSIONS
  This study suggests that the safety profile of everolimus is acceptable in patients with either mRCC or pNET. In addition, the onset of toxicities is associated with an improved DCR. In patients with biliary tract cancer, everolimus is safe but associated with a higher incidence of adverse events.
authors.affiliation: Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G Venezian 1, Milan, 20133, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Verzoni
authors.forename: Sara
authors.initials: S
authors.lastname: Pusceddu
authors.forename: Roberto
authors.initials: R
authors.lastname: Buzzoni
authors.forename: Enrico
authors.initials: E
authors.lastname: Garanzini
authors.forename: Angela
authors.initials: A
authors.lastname: Damato
authors.forename: Pamela
authors.initials: P
authors.lastname: Biondani
authors.forename: Isabella
authors.initials: I
authors.lastname: Testa
authors.forename: Paolo
authors.initials: P
authors.lastname: Grassi
authors.forename: Emilio
authors.initials: E
authors.lastname: Bajetta
authors.forename: Filippo
authors.initials: F
authors.lastname: de Braud
authors.forename: Filippo
authors.initials: F
authors.lastname: DeBraud
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Procopio
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary; D000068338:Everolimus; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000068338:Everolimus; D020123:Sirolimus
keywords: biliary tract cancer; everolimus; mRCC; pNET; safety