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Peripheral neuropathy: a persisting challenge in paclitaxel-based regimes
Stephan Mielke1, Alex Sparreboom, Klaus Mross
1Department of Hematology and Oncology, University of Freiburg Medical Center, Freiburg i. Br., Germany. mielkes@nhlbi.nih.gov
European Journal of Cancer (Oxford, England : 1990)
|November 19, 2005
Summary
Paclitaxel (PAC) can cause cumulative peripheral neuropathy (PNP), limiting treatment. Research reviews PAC-induced PNP
Area of Science:
- Neuroscience
- Oncology
- Pharmacology
Background:
- Peripheral neuropathy (PNP) is a dose-limiting toxicity of paclitaxel (PAC) chemotherapy.
- The exact mechanisms of PAC-induced PNP remain unclear, with both PAC and its vehicle (Cremophor EL) implicated.
Purpose of the Study:
- To review and discuss the pathogenesis, incidence, risk factors, diagnosis, pharmacodynamics, and treatment of PAC-induced PNP.
- To highlight the need for screening tools due to limited treatment options.
Main Methods:
- Literature review of preclinical models and clinical trials.
- Analysis of data on PAC and Cremophor EL effects on neurotoxicity.
Main Results:
- Both PAC and its vehicle contribute to PNP, with PAC's effect potentially linked to microtubule disturbances.
- Even Cremophor EL-free formulations show significant neurotoxicity, indicating PAC's independent role.
- Grade III neurotoxicity remains a dose-limiting factor.
Conclusions:
- Paclitaxel-induced peripheral neuropathy is a significant clinical challenge.
- Understanding PNP mechanisms and risk factors is crucial for patient management.
- Screening systems are recommended for early detection and management of PAC-induced PNP.