title: Peripheral neurotoxicity of weekly paclitaxel chemotherapy: a schedule or a dose issue?
abstract: OBJECTIVE
  The rationale for intensification strategies is that more frequent exposure to chemotherapeutics could enhance antitumor activity. Several trials investigated weekly paclitaxel administration, but there are no clear data concerning peripheral neurotoxicity. The aim of this study was to assess the incidence of peripheral neurotoxicity in patients affected by advanced breast cancer treated with weekly paclitaxel.
  
  
  METHODS
  Neurotoxicity was assessed with neurologic and neurophysiologic evaluation before treatment and after 12 weeks and 24 weeks. A total neurotoxicity score was assigned to each patient on the basis of neurophysiologic and neuropathic signs and symptom changes. Seventeen patients entered the study.
  
  
  RESULTS
  After 12 weeks of treatment, 71% showed moderate clinical and/or neurophysiologic signs of neurotoxicity; after 24 weeks, the incidence of neurotoxicity increased to 96%. Sural amplitude at the 24-weeks examination significantly decreased from basal mean value (13.5 microv, standard deviation [SD] 6 microv vs. 7 microv, SD 5.9 microv, respectively; P = 0.01), whereas median sensory amplitude decreased after 24 weeks from 10.3 microv, SD 6.2 microv to 4.9 microv, SD 3.8 microv (P = 0.001). In a subset of 11 patients, we obtained a follow-up examination after 6 months from the end of treatment. In all patients, examined signs and symptoms of neurotoxicity improved with recovery of subjective neuropathic symptoms and neurophysiologic findings.
  
  
  CONCLUSIONS
  Our results demonstrate, in a little population of patients evaluated with a comprehensive neurologic assessment, that weekly paclitaxel is related to a very high incidence of peripheral neurotoxicity. Follow-up data obtained in a subset of patients indicate that peripheral neurotoxicity is reversible.
authors.affiliation: Department of Neurology, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pace
authors.forename: Cecilia
authors.initials: C
authors.lastname: Nisticò
authors.forename: Federica
authors.initials: F
authors.lastname: Cuppone
authors.forename: Emilio
authors.initials: E
authors.lastname: Bria
authors.forename: Edvina
authors.initials: E
authors.lastname: Galiè
authors.forename: Giuliana
authors.initials: G
authors.lastname: Graziano
authors.forename: Guido
authors.initials: G
authors.lastname: Natoli
authors.forename: Isabella
authors.initials: I
authors.lastname: Sperduti
authors.forename: Bruno
authors.initials: B
authors.lastname: Jandolo
authors.forename: Francesca
authors.initials: F
authors.lastname: Calabretta
authors.forename: Silverio
authors.initials: S
authors.lastname: Tomao
authors.forename: Edmondo
authors.initials: E
authors.lastname: Terzoli
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000453:epidemiology*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel