From bench to bedside: Attempt to evaluate repositioning of drugs in the treatment of metastatic small cell lung cancer (SCLC)

Zoltan Lohinai, Peter Dome, Zsuzsa Szilagyi, Gyula Ostoros, Judit Moldvay, Balazs Hegedus, Balazs Dome, Glen J. Weiss

Research output: Article

11 Citations (Scopus)

Abstract

Backgrounds: 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.

Original languageEnglish
Article numbere0144797
JournalPloS one
Volume11
Issue number1
DOIs
Publication statusPublished - jan. 6 2016

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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