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Epothilone
Epothilones are compounds that induce their cytotoxic effect as
they target the microtubules (mitotic complex) in a way
similar to Taxanes.
They typically bind to B tubulin arresting cells in G2/M
phase
Experimental trials showed that:
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These compounds are active in cell lines resistant to
Taxanes hence no cross
resistance and they can be used upon
Taxanes failure.
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These compounds are active in cells expressing the MDR gene
responsible for
Taxanes
resistance.
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They exert synergism with Trastuzumab.
Ixabepilone, an Epothilone compound was studied in a
phase II study of previously treated advanced breast cancer
patients (NCI 0229).
Patients were treated with a single agent Ixabepilone and
results were so promising as regard to results in heavily
pretreated patients.
The partial response rate was 43% in Taxane
naïve patients.
And 22% including 3 % CR in patients previously
treated with Taxanes who showed also SD of 38%.
Ixabepilone is currently studied in a phase III study ECOG 2103
as first line therapy in combination with Carboplatin and
Trastuzumab.
Another Epothilone compound, EPO 906- patupilone is also
currently on phase III studies again in breast cancer patients.
References:
Low JA et al JCO 2005.
Abbreviations:
CR Complete remission
PR partial remission
SD stable disease.
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