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Lani · 06-12-2009, 05:29 PM

9/11/08 2:10 PM
Sagopilone crosses the blood-brain barrier in vivo...[Neuro Oncol. 2008] - PubMed Result
Page 1 of 1
http://www.ncbi.nlm.nih.gov.laneprox...ubmed_RVDocSum
1: Neuro Oncol. 2008 Sep 9. [Epub ahead of print]
PMID: 18780814 [PubMed - as supplied by publisher]
Sagopilone crosses the blood-brain barrier in vivo to inhibit brain tumor
growth and metastases.
Hoffmann J, Fichtner I, Lemm M, Lienau P, Hess-Stumpp H,
Rotgeri A, Hofmann B, Klar U.
Bayer Schering Pharma AG, TRG Oncology, Müllerstrasse 172178, 13342 Berlin,
Germany.
The aim of this study was to determine the efficacy of sagopilone
(ZK-EPO), a novel epothilone, compared with other anticancer agents
in human orthotopic models of 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 510 mg/kg, paclitaxel 812.5 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
human glioblastoma models, while paclitaxel showed a limited effect
in the U373 model. Sagopilone significantly inhibited the growth of
tumors from CNS metastases 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.

06-12-2009, 05:29 PM	#20
Lani Senior Member Join Date: Mar 2006 Posts: 4,778	Sagopilone ( a relative of Ixempra) 9/11/08 2:10 PM Sagopilone crosses the blood-brain barrier in vivo...[Neuro Oncol. 2008] - PubMed Result Page 1 of 1 http://www.ncbi.nlm.nih.gov.laneprox...ubmed_RVDocSum 1: Neuro Oncol. 2008 Sep 9. [Epub ahead of print] PMID: 18780814 [PubMed - as supplied by publisher] Sagopilone crosses the blood-brain barrier in vivo to inhibit brain tumor growth and metastases. Hoffmann J, Fichtner I, Lemm M, Lienau P, Hess-Stumpp H, Rotgeri A, Hofmann B, Klar U. Bayer Schering Pharma AG, TRG Oncology, Müllerstrasse 172178, 13342 Berlin, Germany. The aim of this study was to determine the efficacy of sagopilone (ZK-EPO), a novel epothilone, compared with other anticancer agents in human orthotopic models of 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 510 mg/kg, paclitaxel 812.5 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 human glioblastoma models, while paclitaxel showed a limited effect in the U373 model. Sagopilone significantly inhibited the growth of tumors from CNS metastases 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.