A phase III randomized, placebo-controlled study of topical amitriptyline and ketamine for chemotherapy-induced peripheral neuropathy (CIPN): a University of Rochester CCOP study of 462 cancer survivors.

Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) occurs in as high as 70% of patients receiving certain types of chemotherapy agents. The FDA has yet to approve a therapy for CIPN. The aim of this multicenter, phase III, randomized, double-blind, placebo-controlled trial was to investigate the efficacy of 2% ketamine plus 4% amitriptyline (KA) cream for reducing CIPN.

Methods: Cancer survivors who completed chemotherapy at least 1 month prior and had CIPN (>4 out of 10) were enrolled (N=462). CIPN was assessed using average scores from a 7-day daily diary that asks patients to rate the average "pain, numbness, or tingling in [their] hands and feet over the past 24 h" on an 11-point numeric rating scale at baseline and 6 weeks post intervention. ANCOVA was used to measure differences in 6-week CIPN with effects including baseline CIPN, KA treatment arm, and previous taxane therapy (Y/N).

Results: The KA treatment showed no effect on 6-week CIPN scores (adjusted mean difference=-0.17, p=0.363).

Conclusions: This study suggests that KA cream does not decrease CIPN symptoms in cancer survivors.