학술논문
A proof-of-concept trial of protein kinase C iota inhibition with auranofin for the paclitaxel-induced acute pain syndrome
Original Article
Original Article
Document Type
Academic Journal
Author
Source
Supportive Care in Cancer. March 2017, Vol. 25 Issue 3, p833, 6 p.
Subject
Language
English
ISSN
0941-4355
Abstract
Author(s): Aminah Jatoi [sup.1] , Megan E. Grudem [sup.1] , Travis J. Dockter [sup.2] , Matthew S. Block [sup.1] , Jose C. Villasboas [sup.1] , Angelina Tan [sup.2] , Erin [...]
Purpose 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. Methods 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." Results 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. Conclusions In the dose schedule studied, auranofin did not palliate the PIAP syndrome, but delayed beneficial trends suggest further study for this indication.
Purpose 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. Methods 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." Results 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. Conclusions In the dose schedule studied, auranofin did not palliate the PIAP syndrome, but delayed beneficial trends suggest further study for this indication.