Antitumor action of temozolomide, ritonavir and aprepitant against human glioma cells

J Neurooncol. 2016 Feb;126(3):425-31. doi: 10.1007/s11060-015-1996-6. Epub 2015 Nov 24.

Abstract

In the effort to find better treatments for glioblastoma we tested several currently marketed non-chemotherapy drugs for their ability to enhance the standard cytotoxic drug currently used to treat glioblastoma- temozolomide. We tested four antiviral drugs- acyclovir, cidofovir, maraviroc, ritonavir, and an anti-emetic, aprepitant. We found no cytotoxicity of cidofovir and discussed possible reasons for discrepancy from previous findings of others. We also found no cytotoxicity from acyclovir or maraviroc also in contradistinction to predictions. Cytotoxicity to glioma cell line GAMG for temozolomide alone was 14%, aprepitant alone 7%, ritonavir alone 14%, while temozolomide + aprepitant was 19%, temozolomide + ritonavir 34%, ritonavir + aprepitant 64 %, and all three, temozolomide + ritonavir + aprepitant 78%. We conclude that a remarkable synergy exists between aprepitant and ritonavir. Given the long clinical experience with these two well-tolerated drugs in treating non-cancer conditions, and the current median survival of glioblastoma of 2 years, a trial is warranted of adding these two simple drugs to current standard treatment with temozolomide.

Keywords: Aprepitant; Combination therapy; Glioblastoma; Ritonavir; Temozolomide.

MeSH terms

  • Antiemetics / pharmacology*
  • Antineoplastic Agents, Alkylating / pharmacology
  • Apoptosis / drug effects
  • Aprepitant
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Cell Proliferation / drug effects*
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / pharmacology
  • Glioblastoma / drug therapy*
  • Glioblastoma / pathology
  • HIV Protease Inhibitors / pharmacology
  • Humans
  • Immunoenzyme Techniques
  • Morpholines / pharmacology*
  • Ritonavir / pharmacology*
  • Temozolomide
  • Tumor Cells, Cultured

Substances

  • Antiemetics
  • Antineoplastic Agents, Alkylating
  • HIV Protease Inhibitors
  • Morpholines
  • Aprepitant
  • Dacarbazine
  • Ritonavir
  • Temozolomide