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 6 41 mg/m2 paclitaxel, 71 % of patients developed neuropathic symptoms by 6 weeks of treat-ment. Early and progressive increases in stimulus threshold (P < 0.05) and reduction in sensory amplitudes from 47.0 6 3.3 lV to 42.4 6 3.4 lV (P < 0.05) occurred by 4 weeks, with a further reduction by final treatment (33.7 6 3.0 lV, P < 0.001). The majority of patients (63%) did not experience recov-ery of neuropathic symptoms at follow-up. Axonal disruption did not relate to membrane conductance dysfunction. We foun