Initial prep showed that formulation, QC, and cost for high-dose paeonol/Cortex Moutan exceeded the budget. Also, recruiting patients with chemotherapy-induced peripheral neuropathy was limited. To ensure safety, enrollment did not officially launch.

A randomized controlled trial was designed and conducted to confirm whether oral administration of the herb Moutan Cortex, which contains paeonol, can alleviate peripheral neuropathy in paclitaxel-treated cancer patients. This research project will validate our new preliminary findings demonstrating the neuroprotective effects after paclitaxel treatment. Importantly, our data are expected to elucidate the way Moutan Cortex induces neuroprotection in the clinical setting and provide a scientific basis for the development of new approaches to treat CIPN.

Chemotherapy-induced peripheral neuropathy (CIPN) is a disabling pain condition that involves structural and functional impairment of peripheral motor, sensory, and autonomic neurons. CIPN symptoms may involve a combination of motor, sensory, and autonomic deficits. Sensory symptoms are the most common and are usually the first to appear, affecting the hands and feet the most. Sensory symptoms usually manifest as spontaneous or induced abnormal sensations, such as abnormal sensation, sensory dullness, numbness, burning, shooting or electric shock sensations, and unusual pain or pain hypersensitivity induced by mechanical or thermal stimuli. Paclitaxel drugs are among the most commonly used neurotoxic chemotherapeutic agents. In the absence of effective conventional treatments, there are limited effective ways to prevent or treat CIPN. The traditional Chinese medicine, Moutan Cortex, has long been used for its anticoagulant, anti-inflammatory, analgesic, and sedative activities, as well as for the treatment of cardiovascular, hemorrhagic, stagnated blood, and female genital disorders. Studies have shown that paeonol, a major component of Moutan Cortex, has analgesic, antipyretic and antibacterial properties, as well as anti-inflammatory, antioxidant and anti-platelet aggregation effects. It has a wide range of properties, such as inhibiting collagen-induced platelet aggregation and attenuating inflammatory responses in airways, coronary arteries, macrophages and microglia. Preliminary results in a baseline study showed that intraperitoneal administration of paclitaxel reduced the mechanical nociceptive threshold in the hind palm, indicating increased sensitivity to painful stimuli (mechanical allodynia pain). In contrast, the reduction in mechanical nociceptive threshold in the hind palm induced by paclitaxel was significantly reversed after oral administration of different doses of dandruff and approached that of the control group without paclitaxel, showing a significant improvement in mechanical anomalous pain. Therefore, a randomized controlled trial was designed and conducted to confirm whether oral administration of the herb Moutan Cortex, which contains paeonol, can alleviate peripheral neuropathy in paclitaxel-treated cancer patients. This research project will validate our new preliminary findings demonstrating the neuroprotective effects after paclitaxel treatment. Importantly, our data are expected to elucidate the way Moutan Cortex induces neuroprotection in the clinical setting and provide a scientific basis for the development of new approaches to treat CIPN.

Inclusion Criteria:

• adult women above 20 years, diagnosed with stage I-III breast cancer by a histological analysis, and who had completed adjuvant or neoadjuvant neurotoxic chemotherapy (including taxane-based or platinum-based), with the severity of CIPN matching the definition of the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) 4.0 version more than grade 1. In addition, the patients' daily physical status will match the definition of the Eastern Cooperative Oncology Group (ECOG) performance status less than grade 3

Exclusion Criteria:

• metastatic breast cancer, a history of diabetic neurological disease before chemotherapy, other pre-existing peripheral neurological disorders, a history of inflammatory or metabolic arthritis, severe coagulopathy or potential bleeding tendency, dermatological disease within acupuncture needling area. Concomitant use of selected analgesics was allowed23 (e.g.,opioids, acetaminophen, aspirin, non-steroidal anti-inflammatory drugs [NSAIDs]), but only patients receiving stable doses in the two weeks prior to randomization could participate: 1) no new analgesics were added; 2) no analgesics were discontinued; and 3) the weekly 24-hour total analgesic dose did not fluctuate up or down by > 10% in the two weeks prior to study registration