Peripheral neuropathy: a persisting challenge in paclitaxel-based regimes.
Cumulative peripheral neuropathy (PNP) still remains a limitation to optimal treatment with paclitaxel (PAC), especially in more dose-dense schedules. This primary sensory PNP may affect the majority of patients after administration of certain cumulative dosages of PAC, while the exact mechanisms of PAC-induced PNP are not known. While a number of preclinical models revealed its vehicle Cremophor EL (CrEL) to be mainly responsible for ganglionopathy, axonopathy and demyelination, clinical data also supports a strong and independent effect of PAC itself, which is most likely based on disturbances in the microtubules in perikaryons, axons and glia cells. Indeed, clinical trials of CrEL-free formulations of PAC still report grade III neurotoxicity as dose-limiting. As treatment options of PAC-induced PNP are rare the use of specific scoring systems for screening purposes is strongly encouraged. In this report we review and discuss the pathogenesis, incidence, risk factors, diagnosis, pharmacodynamics and treatment options for PAC-induced PNP.
Mielke
Stephan
S
Department of Hematology and Oncology, University of Freiburg Medical Center, Freiburg i. Br., Germany. mielkes@nhlbi.nih.gov
Sparreboom
Alex
A
Mross
Klaus
K
D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects* / Q000493:pharmacokinetics; D006801:Humans; D017239:Paclitaxel / Q000009:adverse effects* / Q000493:pharmacokinetics; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000517:prevention & control; D014677:Pharmaceutical Vehicles / Q000009:adverse effects; D011092:Polyethylene Glycols / Q000009:adverse effects; D011379:Prognosis; D012307:Risk Factors
D000972:Antineoplastic Agents, Phytogenic; D014677:Pharmaceutical Vehicles; D011092:Polyethylene Glycols; D017239:Paclitaxel; C018557:glycofurol