Sagopilone crosses the blood-brain barrier in vivo to inhibit brain tumor growth and metastases

Neuro Oncol. 2009 Apr;11(2):158-66. doi: 10.1215/15228517-2008-072. Epub 2008 Sep 9.


The aim of this study was to determine the efficacy of sagopilone (ZK-EPO), a novel epothilone, compared with other anticancer agents in orthotopic models of human primary and secondary brain tumors. Autoradiography and pharmacokinetic analyses were performed on rats and mice to determine passage across the blood-brain barrier and organ distribution of sagopilone. Mice bearing intracerebral human tumors (U373 or U87 glioblastoma, MDA-MB-435 melanoma, or patient-derived non-small-cell lung cancer [NSCLC]) were treated with sagopilone 5-10 mg/kg, paclitaxel 8-12.5 mg/kg (or temozolomide, 100 mg/kg) or control (vehicle only). Tumor volume was measured to assess antitumor activity. Sagopilone crossed the blood-brain barrier in both rat and mouse models, leading to therapeutically relevant concentrations in the brain with a long half-life. Sagopilone exhibited significant antitumor activity in both the U373 and U87 models of human glioblastoma, while paclitaxel showed a limited effect in the U373 model. Sagopilone significantly inhibited the growth of tumors from CNS metastasis models (MDA-MB-435 melanoma and patient-derived Lu7187 and Lu7466 NSCLC) implanted in the brains of nude mice, in contrast to paclitaxel or temozolomide. Sagopilone has free access to the brain. Sagopilone demonstrated significant antitumor activity in orthotopic models of both glioblastoma and CNS metastases compared with paclitaxel or temozolomide, underlining the value of further research evaluating sagopilone in the treatment of brain tumors. Sagopilone is currently being investigated in a broad phase II clinical trial program, including patients with glioblastoma, NSCLC, breast cancer, and melanoma.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Alkylating / pharmacokinetics
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Antineoplastic Agents, Phytogenic / pharmacokinetics
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Benzothiazoles / pharmacokinetics*
  • Benzothiazoles / therapeutic use
  • Blood-Brain Barrier*
  • Brain / metabolism*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Dacarbazine / analogs & derivatives
  • Dacarbazine / pharmacokinetics
  • Dacarbazine / therapeutic use
  • Epothilones / pharmacokinetics*
  • Epothilones / therapeutic use
  • Female
  • Half-Life
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Paclitaxel / pharmacokinetics
  • Paclitaxel / therapeutic use
  • Rats
  • Rats, Wistar
  • Survival Rate
  • Temozolomide
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents, Alkylating
  • Antineoplastic Agents, Phytogenic
  • Benzothiazoles
  • Epothilones
  • Dacarbazine
  • sagopilone
  • Paclitaxel
  • Temozolomide