Breast Cancer, Chemotherapy-induced Peripheral Neuropathy (CIPN)
Conditions
Keywords
chemotherapy-induced peripheral neuropathy, paclitaxel, Moutan Cortex, neuropathic pain
Brief summary
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.
Detailed description
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.
Interventions
DRUGMoutan cortex
Moutan Cortex, the certified pharmaceutical name is "Moutan radices extract power". The purchased powder is manufactured by Sheng Chang Pharmaceutical Co. Ltd., Taoyuan, Taiwan (No. 0714A) and standardized with a standard product of Moutan Cortex certified by Taiwan Food and Drug Administration (certified no. 003053).
DRUGsham moutan cortex
The sham Moutan cortex powder will also be manufactured by Sheng Chang Pharmaceutical Co. Ltd., Taoyuan, Taiwan. Each participant will intake sham moutan cortex 2g/day daily for 4 weeks.
Sponsors
Taiwan Municipal An-Nan Hospital-China Medical University
China Medical University, Taiwan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| BPI-SF;the Brief Pain Inventory-Short Form | BPI-SF will be assessed at the end of chemotherapy (baseline; the 0 week), and at the end of intervention (the 4th week) | The primary endpoint was the mean of mean change in the average pain severity between groups. The two arms will measure the average pain severity score of the Brief Pain Inventory-Short Form24 (BPI-SF) at the 4th week. The BPI-SF average pain severity score uses a 0-10 scale for subject ratings. The items range from 0 to 10 (0 = no pain; 10 = worst pain). The higher the pain severity scores, the worse the degree of pain experienced by the patient. The BPI-SF also measures the pain interference on seven daily functions during the past 24 h, including general activities, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Using numeric scales, the items range from 0 to 10 (0 = no interference; 10= interferes completely). This study will measure the average pain severity and seven pain interference domains for eligible participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SWM | SWM will be assessed at the end of chemotherapy (baseline; the 0 week), and at the end of intervention (the 4th week) | von Frey monofilaments (Semmes-Weinstein von Frey Aesthesiometer, Stoelting Co., Wood Dale, IL, USA):a set of 20 von Frey monofilaments with evaluator size/target forces ranging from 1.65/0.008 g to 6.65/300 g. Each monofilament was calibrated to a target force in grams (g) within a 5% standard deviation. Measurement sites included the sole, tip of the big toe, palm, and tip of the middle finger. All tests were performed by an independent assessor who was blinded to the allocation of randomization. All the procedures followed the operation manual provided by the filament manufacturer. |
| The 13-item FACT/GOG-Ntx subscale | FACT/GOG-Ntx subscale will be assessed at the end of chemotherapy (baseline; the 0 week), and at the end of intervention (the 4th week) | The 13-item FACT/GOG-Ntx subscale26 measures the severity and impact of neurotoxicity symptoms over the past seven days. The instrument assesses sensory symptoms, such as numbness, tingling, and discomfort in hands and feet, motor symptoms such as trouble walking, buttoning buttons, and ototoxicity, such as ringing or buzzing in the ear. Items are rated on a five-point scale, scored from 0 to 4 (0 = not at all; 4 = very much) and summed (total score range = 0-52). Higher scores on the neurotoxicity scale indicate improvements in neurotoxic symptoms. |
Countries
Taiwan
Outcome results
None listed