title: Early, progressive, and sustained dysfunction of sensory axons underlies paclitaxel-induced neuropathy.
abstract: Paclitaxel is used in the adjuvant treatment of breast cancer. It induces disabling and potentially long-lasting sensory neuropathy. This study systematically and prospectively investigated sensory function, using clinical grading scales, quantitative sensory testing, and neurophysiological and nerve excitability studies in 28 patients with early-stage breast cancer. After administration of 529 ± 41 mg/m(2) paclitaxel, 71% of patients developed neuropathic symptoms by 6 weeks of treatment. Early and progressive increases in stimulus threshold (P < 0.05) and reduction in sensory amplitudes from 47.0 ± 3.3 μV to 42.4 ± 3.4 μV (P < 0.05) occurred by 4 weeks, with a further reduction by final treatment (33.7 ± 3.0 μV, P < 0.001). The majority of patients (63%) did not experience recovery of neuropathic symptoms at follow-up. Axonal disruption did not relate to membrane conductance dysfunction. We found that paclitaxel produces early sensory dysfunction and leads to persistent neuropathy. Importantly, significant axonal dysfunction within the first month of treatment predated symptom onset, suggesting a window for neuroprotective therapies.
authors.affiliation: Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Susanna B
authors.initials: SB
authors.lastname: Park
authors.forename: Cindy S-Y
authors.initials: CS
authors.lastname: Lin
authors.forename: Arun V
authors.initials: AV
authors.lastname: Krishnan
authors.forename: Michael L
authors.initials: ML
authors.lastname: Friedlander
authors.forename: Craig R
authors.initials: CR
authors.lastname: Lewis
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Kiernan
mesh_terms: D000328:Adult; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008875:Middle Aged; D017239:Paclitaxel / Q000009:adverse effects*; D011115:Polyneuropathies / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology*; D011446:Prospective Studies; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
chemical_list: D017239:Paclitaxel