Shakuyakukanzoto for Paclitaxel‐Induced Myalgia and Arthralgia: A Placebo‐Controlled Crossover Trial

ABSTRACT Aim Paclitaxel causes myalgia and arthralgia in 20%–60% of patients. Shakuyakukanzoto (SKT, Shao‐Yao‐Gan‐Cao‐Tang), a traditional Chinese herbal formula comprising peony and licorice, has been used to relieve pain in Japan. Herein, we conducted a placebo‐controlled crossover study to evaluate shakuyakukanzoto's efficacy and safety against paclitaxel‐induced toxicity. Methods This study is a single‐center, placebo‐controlled, double‐blind crossover trial of shakuyakukanzoto. Participants were randomly assigned (1:1) and received 7 days of shakuyakukanzoto or placebo in random order. The pain scale was based on Common Terminology Criteria for Adverse Events. Results Twenty‐two patients were enrolled. From Days 3 to 5, the maximum pain, maximum pain scale, or average pain scale did not differ significantly between the shakuyakukanzoto and placebo groups. However, the mean change in number of days with 2 or more pain rates from Days 3 to 5 during paclitaxel administration between the screening period and the placebo group differed significantly. Shakuyakukanzoto did not affect paclitaxel metabolism, while shakuyakukanzoto metabolites were detected in the next course. Conclusion We evaluated the potential alleviating effect of shakuyakukanzoto on paclitaxel‐mediated myalgia and arthralgia. No significant alleviating effect of shakuyakukanzoto was noted when compared to placebo. A study design using placebo during the run‐in period is necessary to minimize the influence of the placebo effect. Trial Registration: Registered on Japan Registry of Clinical Trials with registration number of jRCT2041210101