title: From Bench to Bedside: Attempt to Evaluate Repositioning of Drugs in the Treatment of Metastatic Small Cell Lung Cancer (SCLC).
abstract: BACKGROUND
  Based on in vitro data and results of a recent drug repositioning study, some medications approved by the FDA for the treatment of various non-malignant disorders were demonstrated to have anti-SCLC activity in preclinical models. The aim of our study is to confirm whether use of these medications is associated with survival benefit.
  
  
  METHODS
  Consecutive patients with pathologically confirmed, stage 4 SCLC were analyzed in this retrospective study. Patients that were prescribed statins, aspirin, clomipramine (tricyclic antidepressant; TCA), selective serotonin reuptake inhibitors (SSRIs), doxazosin or prazosin (α1-adrenergic receptor antagonists; ADRA1) were identified.
  
  
  RESULTS
  There were a total of 876 patients. Aspirin, statins, SSRIs, ADRA1, and TCA were administered in 138, 72, 20, 28, and 5 cases, respectively. A statistically significant increase in median OS was observed only in statin-treated patients when compared to those not receiving any of the aforementioned medications (OS, 8.4 vs. 6.1 months, respectively; p = 0.002). The administration of SSRIs, aspirin, and ADRA1 did not result in a statistically significant OS benefit (median OS, 8.5, 6.8, and 6.0 months, respectively). The multivariate Cox model showed that, besides age and ECOG PS, radiotherapy was an independent survival predictor (Hazard Ratio, 2.151; 95% confidence interval, 1.828-2.525; p <0.001).
  
  
  CONCLUSIONS
  Results of drug repositioning studies using only preclinical data or small numbers of patients should be treated with caution before application in the clinic. Our data demonstrated that radiotherapy appears to be an independent survival predictor in stage 4 SCLC, therefore confirming the results of other prospective and retrospective studies.
authors.affiliation: National Koranyi Institute of Pulmonology, Budapest, Hungary.|Western Regional Medical Center, Cancer Treatment Centers of America, Goodyear, Arizona, United States of America.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Lohinai
authors.affiliation: Department of Clinical and Theoretical Mental Health, Kútvölgyi Clinical Center, Semmelweis University, Budapest, Hungary.|National Institute of Psychiatry and Addictions, Budapest, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Dome
authors.affiliation: National Koranyi Institute of Pulmonology, Budapest, Hungary.
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Szilagyi
authors.affiliation: National Koranyi Institute of Pulmonology, Budapest, Hungary.
authors.forename: Gyula
authors.initials: G
authors.lastname: Ostoros
authors.affiliation: National Koranyi Institute of Pulmonology, Budapest, Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Moldvay
authors.affiliation: Translational Thoracic Oncology Laboratory, Division of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.|Molecular Oncology Research Group, Hungarian Academy of Sciences-Semmelweis University, Budapest, Hungary.
authors.forename: Balazs
authors.initials: B
authors.lastname: Hegedus
authors.affiliation: National Koranyi Institute of Pulmonology, Budapest, Hungary.|Translational Thoracic Oncology Laboratory, Division of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.|Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria.
authors.forename: Balazs
authors.initials: B
authors.lastname: Dome
authors.affiliation: Western Regional Medical Center, Cancer Treatment Centers of America, Goodyear, Arizona, United States of America.
authors.forename: Glen J
authors.initials: GJ
authors.lastname: Weiss
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use; D058492:Drug Repositioning / Q000706:statistics & numerical data*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000737:chemistry / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D055752:Small Cell Lung Carcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*
chemical_list: D000970:Antineoplastic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors