Taxane neuropathy: clinical features, mechanisms and methods of assessment.
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Associate Professor Arun Krishnan Translational Neuroscience Facility, University of New South Wales & Department of Neurology, Prince of Wales Hospital, Sydney Taxane neuropathy: clinical features, mechanisms and methods of assessment
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Transcript of Taxane neuropathy: clinical features, mechanisms and methods of assessment.
Associate Professor Arun Krishnan
Translational Neuroscience Facility, University of New South Wales & Department of Neurology, Prince of Wales Hospital, Sydney
Taxane neuropathy: clinical features, mechanisms and methods of
assessment
Paclitaxel Dose-dependent distal sensory neuropathy with
numbness and paresthesia in extremities Motor involvement in severe cases Symptoms may be long-lasting
Proposed mechanisms include disruption of axonal transport
Park et al., 2008 Curr Med Chem
Park et al., 2008 Curr Med Chem
Park et al., 2008 Curr Med Chem
• 71% reported neuropathic symptoms• Developed after mean of 6 weeks of treatment• Most reported simultaneous onset UL and LL symptoms• 63% reported no improvement at follow-up
None Asymptomatic; loss of deep tendon reflexes or paresthesia (including tingling) but not interfering with function
Sensory alteration or paresthesia (including tingling), interfering with function, but not interfering with ADL
Sensory alteration of paresthesia interfering with ADL
Disabling
0 1 2 3 4
National Cancer Institute – Common Toxicity Criteria for Adverse Events
Nerve Conduction Studies Conventional nerve conduction studies
(NCS) use supramaximal stimuli to assess:
Amplitude (= number conducting fibres)
Latency (= the velocity of the fastest fibres)
demyelinating
axonal
Oxaliplatin vs. Paclitaxel Differences in time course of CSAP decline
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Baseline Month 1 Month 2 Month 3 Final
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pea
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Oxaliplatin
Paclitaxel
‘Coasting’
Axonal transport dysfunction?
Park et al. 2010 Muscle & Nerve
Nerve Excitability Testing Novel threshold tracking techniques
Evaluates determinants of membrane potential and ion channel function in vivo
Parameters sensitive to change prior to axonal loss
Assess both motor and sensory function
STIMULATING
RECORDING
Initial Treatment
Final Treatment
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(%)
TEh 90-100ms
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RefractorinessSuperexcitability
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PACLITAXEL
OXALIPLATIN
Acknowledgements
Neurology Matthew Kiernan Susanna Park Cindy Lin Jenna Murray Hannah Pickering
Medical Oncology Michael Friedlander David Goldstein
NHMRC
