title: A proof-of-concept trial of protein kinase C iota inhibition with auranofin for the paclitaxel-induced acute pain syndrome.
abstract: Paclitaxel causes the paclitaxel-induced acute pain (PIAP) syndrome. Based on preclinical data, we hypothesized that the protein kinase C (PKC) iota inhibitor, auranofin (a gold salt used for other pain conditions), palliates this pain.
  
  
  
  In a randomized, double-blinded manner, patients who had suffered this syndrome were assigned a one-time dose of auranofin 6 mg orally on day #2 of the chemotherapy cycle (post-paclitaxel) versus placebo. Patients completed the Brief Pain Inventory and a pain diary on days 2 through 8 and at the end of the cycle. The primary endpoint was pain scores, as calculated by area under the curve, in response to "Please rate your pain by circling the one number that best describes your pain at its worse in the last 24 hours."
  
  
  
  Thirty patients were enrolled. For the primary endpoint, mean area under the curve of 55 units (standard deviation 19) and 61 units (standard deviation 22) were observed in auranofin-treated and placebo-exposed patients, respectively (p = 0.44). On day 8 and at the end of the cycle, pain scores in auranofin-treated patients were more favorable, although differences were not statistically significant.
  
  
  
  In the dose schedule studied, auranofin did not palliate the PIAP syndrome, but delayed beneficial trends suggest further study for this indication.
authors.affiliation: Department of Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. jatoi.aminah@mayo.edu.
authors.forename: Aminah
authors.initials: A
authors.lastname: Jatoi
authors.affiliation: Department of Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Grudem
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: Travis J
authors.initials: TJ
authors.lastname: Dockter
authors.affiliation: Department of Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Block
authors.affiliation: Department of Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
authors.forename: Jose C
authors.initials: JC
authors.lastname: Villasboas
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: Angelina
authors.initials: A
authors.lastname: Tan
authors.affiliation: Department of Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Deering
authors.affiliation: Department of Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
authors.forename: Pashtoon M
authors.initials: PM
authors.lastname: Kasi
authors.affiliation: Department of Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Mansfield
authors.affiliation: Department of Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
authors.forename: Juliana Perez
authors.initials: JP
authors.lastname: Botero
authors.affiliation: Department of Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
authors.forename: Scott H
authors.initials: SH
authors.lastname: Okuno
authors.affiliation: Department of Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
authors.forename: Deanne R
authors.initials: DR
authors.lastname: Smith
authors.affiliation: Cancer Biology, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Alan P
authors.initials: AP
authors.lastname: Fields
mesh_terms: D059787:Acute Pain / Q000139:chemically induced* / Q000188:drug therapy* / Q000201:enzymology; D000284:Administration, Oral; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000627:therapeutic use; D001310:Auranofin / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000009:adverse effects* / Q000627:therapeutic use; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000188:drug therapy; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D013577:Syndrome; D000099293:Protein Kinase C-lambda
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001310:Auranofin; D007527:Isoenzymes; D017239:Paclitaxel; D011493:Protein Kinase C; D047428:Protein Kinase Inhibitors; D000099293:Protein Kinase C-lambda
keywords: Auranofin; Myalgias; Protein kinase C