title: A randomized, double-blinded, placebo-controlled phase II trial of recombinant human leukemia inhibitory factor (rhuLIF, emfilermin, AM424) to prevent chemotherapy-induced peripheral neuropathy.
abstract: OBJECTIVE
  To determine whether recombinant human leukemia inhibitory factor (rhuLIF, AM424, emfilermin) can prevent or ameliorate the development of chemotherapy-induced peripheral neuropathy (CIPN) after treatment with carboplatin (AUC 6) and paclitaxel (175 mg/m(2) over 3 hours).
  
  
  METHODS
  Randomized double-blind placebo-controlled phase II clinical trial. Eligible patients had solid tumors for which treatment with carboplatin/paclitaxel was appropriate. The primary end point was a standardized composite peripheral nerve electrophysiology (CPNE) score, based on nerve velocities and amplitudes, measured at baseline and after four cycles of chemotherapy. Secondary efficacy end points included CPNE score at last cycle and at exit evaluation, vibration perception threshold, H-reflex latency, symptom scores, and quantitative assessment of neurologic signs. Study drug was given s.c. daily for 7 days starting the day before chemotherapy. Patients were randomized to receive low-dose rhuLIF (2 microg/kg), high-dose rhuLIF (4 microg/kg), or placebo.
  
  
  RESULTS
  Patients (n = 117) were randomized across seven neurology test centers. Thirty-six patients received low dose rhuLIF (2 microg/kg), 39 received high dose rhuLIF (4 microg/kg) and 42 received placebo. rhuLIF was well tolerated with 95% compliance and no adverse effects on quality of life. No differences between groups in CPNE or any of the individual neurologic testing variables were observed between baseline and cycle 4 or by the secondary efficacy variables.
  
  
  CONCLUSIONS
  rhuLIF is not effective in preventing CIPN caused by carboplatin and paclitaxel. CPNE is a reliable and valid tool that was sensitive to the onset and progression of CIPN.
authors.affiliation: Austin Health, Studley Road, Heidelberg, Victoria 3084, Australia. Ian.Davis@ludwig.edu.au
authors.forename: Ian D
authors.initials: ID
authors.lastname: Davis
authors.forename: Lynette
authors.initials: L
authors.lastname: Kiers
authors.forename: Lachlan
authors.initials: L
authors.lastname: MacGregor
authors.forename: Michael
authors.initials: M
authors.lastname: Quinn
authors.forename: Joseph
authors.initials: J
authors.lastname: Arezzo
authors.forename: Michael
authors.initials: M
authors.lastname: Green
authors.forename: Mark
authors.initials: M
authors.lastname: Rosenthal
authors.forename: Michael
authors.initials: M
authors.lastname: Chia
authors.forename: Michael
authors.initials: M
authors.lastname: Michael
authors.forename: Peter
authors.initials: P
authors.lastname: Bartley
authors.forename: Leonie
authors.initials: L
authors.lastname: Harrison
authors.forename: Michael
authors.initials: M
authors.lastname: Daly
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D016207:Cytokines; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008049:Lipase; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D009431:Neural Conduction; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D010919:Placebos; D011446:Prospective Studies; D011506:Proteins / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D016207:Cytokines; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D010919:Placebos; D011506:Proteins; D016190:Carboplatin; D008049:Lipase; D017239:Paclitaxel