Peripheral neuropathy due to paclitaxel: study of the temporal relationships between the therapeutic schedule and the clinical quantitative score (QST) and comparison with neurophysiological findings

Abstract

Peripheral neuropathy (PN) is one of the most common and dose-limiting side effects of paclitaxel, a chemiotherapeutic drug of proven efficacy in various tumours. We investigated the pathophysiological features of the PN and the temporal relationships between the development of the symptoms and signs associated with paclitaxel administration in two groups of patients with breast cancer: group A received paclitaxel alone (total cumulative dose range: 950-2,475 mg/m2), and group B paclitaxel and adriamycin (total cumulative dose range: 700-2,800 mg/m2). A codified assessment scoring clinical sensory and motor functions according to the Common Toxicity Scale and neurophysiological measurements were made before treatment, after the third and sixth cycles, and at the end of therapy. A total neuropathy score (TNS) included selected clinical and neurophysiological parameters. Both positive and negative sensory and motor symptoms and signs of PN developed during therapy, the most common being painful paresthesias, global areflexia and distal weakness. The neurophysiological study showed an early onset, length-independent and progressive sensory defect, and delayed, distal and length-dependent motor deficits. The neuropathy progressed faster in group A than in group B but, after therapy, most of the patients were TNS grade 2 regardless of their group. The temporal relationships between the PN and paclitaxel were robustly characterised, and thus provide reference data and a model for testing the efficacy of drugs designed to provide neuroprotection.