Pilot Study of Minocycline for the Prevention of Paclitaxel-Associated Neuropathy: ACCRU RU221408I (FR420C)

Abstract

•Understand the results of this pilot study of minocycline for the prevention of P-APS and CIPN.•Gain knowledge of the potential effect of minocycline for prevention of fatigue in patients treated with paclitaxel. Paclitaxel is associated with both an acute pain syndrome (P-APS) and chronic chemotherapy-induced peripheral neuropathy (CIPN). Preliminary animal data suggest that minocycline may be effective for the prevention of chemotherapy-induced neurotoxicity. The primary goal of this study was to obtain pilot data regarding the possible effect of minocycline on the prevention of paclitaxel-induced CIPN and P-APS, to determine if conducting a larger phase III placebo-controlled trial was indicated. Patients with breast cancer were enrolled prior to initiating neoadjuvant or adjuvant weekly paclitaxel for 12 weeks. They were randomized to receive minocycline 200mg on day 1 followed by 100mg twice daily or a placebo, with the same dosing schedule. Patients completed 1) an acute pain syndrome questionnaire daily during chemotherapy, and 2) the EORTC QLQ-CIPN20 questionnaire at baseline, prior to each dose of paclitaxel, and monthly for 6 months post treatment. Scores obtained from patient questionnaires were converted to a 0-100 scale, where higher scores = better quality of life. Forty-seven patients were randomized, 45 of which were evaluable, with a mean age of 55. There were no remarkable differences noted between the two groups for the overall sensory score of the EORTC-CIPN 20 or its individual sub-questions, which evaluated tingling, numbness, or shooting burning pain in hands and feet. However, there was a significant difference in the daily average AUC pain score attributed to P-APS, favoring minocycline (median 96.0 vs 84.3; p=0.02). Correspondingly, patients receiving minocycline used less opioid pain medications for control of P-APS (0% vs 23%, P=0.05). Not only were no increased toxicities reported with minocycline, but there was an apparent improvement in fatigue (median AUC 76.7 vs 59.0; P= 0.02). Based on the results of this pilot study, minocycline did not appear to be beneficial for the prevention of CIPN, but did look promising for reducing P-APS. Further study of this effect maybe warranted.