title: Phase II study evaluating efficacy and safety of everolimus with letrozole for management of advanced (unresectable or metastatic) non-small cell lung cancer after failure of platinum-based treatment: a preliminary analysis of toxicity.
abstract: BACKGROUND
  Lung cancer is one of the most common malignancies worldwide. Non-small cell lung cancer (NSCLC) comprises the majority of the cases of lung cancer. Previous studies have demonstrated a role for both the estrogen pathway and mammalian target of rapamycin (mTOR) in NSCLC.
  
  
  METHODS
  This single-arm phase 2 study was designed to assess the safety and efficacy of combination treatment with aromatase inhibitor—letrozole—and mTOR inhibitor—everolimus—in the treatment of patients with advanced (unresectable stage III or stage IV) NSCLC who had failed at least one line of platinum-based chemotherapy.
  
  
  RESULTS
  The study was closed after enrolling five patients due to safety concerns. Of the five patients treated with the study combination, two patients developed grade 5 pulmonary toxicity and another patient developed reversible grade 4 pulmonary toxicity.
  
  
  CONCLUSIONS
  There is a probable causal relationship between the study medication and the reported serious adverse events. In the absence of additional clinical data in lung cancer patients, we recommend that extreme caution be exercised in the use of combined letrozole and everolimus regimens in patients with advanced lung cancers, active pulmonary pathologies, or both.
authors.affiliation: Department of Medical Oncology, Royal Adelaide Hospital, Adelaide, SA, 5000, Australia, Nimit.Singhal@health.sa.gov.au.
authors.forename: Nimit
authors.initials: N
authors.lastname: Singhal
authors.forename: Sina
authors.initials: S
authors.lastname: Vatandoust
authors.forename: Michael P
authors.initials: MP
authors.lastname: Brown
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D000068338:Everolimus; D005260:Female; D006801:Humans; D000077289:Letrozole; D008171:Lung Diseases / Q000139:chemically induced; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives; D012907:Smoking / Q000009:adverse effects; D014230:Triazoles / Q000008:administration & dosage
chemical_list: D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D009570:Nitriles; D009944:Organoplatinum Compounds; D014230:Triazoles; D000077289:Letrozole; D000068338:Everolimus; D020123:Sirolimus