Prevention of Taxane-associated Acute Pain Syndrome With Etoricoxib

Study Overview
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Brief Summary
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A phase II randomized clinical trial was conducted to determine whether etoricoxib could prevent or ameliorate the incidence and/or severity of docetaxel-induced acute pain syndrome. We also aimed to determine if there are any improvement of the late-onset peripheral neuropathy as well as quality of life with prophylactic etoricoxib for breast cancer patients who receive docetaxel chemotherapy.

Detailed Description
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Docetaxel plays a key role in reducing the recurrence of early-stage breast cancer as well as improving survival outcomes of advanced breast cancer patients, but it causes a variety of adverse events, including myalgia and arthralgia, peripheral neuropathy, febrile neutropenia, and hypersensitivity reactions and so on. The myalgia and arthralgia induced by docetaxel, which have been together referred to as taxane-associated acute pain syndrome (T-APS), were reported to occur in 3.6% to 70% of patients, and the symptoms usually occurred 24-48 hours after docetaxel infusion and lasted for 3-5 days. Previous studies found that patients who experienced myalgia and arthralgia due to docetaxel administration were more likely to have chronic peripheral neuropathy, which supported that T-APS could be a form of neurologic toxicity. T-APS may significantly influence patients' sleep and daily life, and even caused discontinuation of chemotherapy. Therefore, it is clinically meaningful to explore some prophylactic drugs for the T-APS. Previous studies had used glutamine, corticosteroids, Shakuyaku-Kanzo-To (a Japanese herb), and gabapentin to prevent paclitaxel-induced myalgia and arthralgia, but failed to provide enough evidence for clinical practice. Etoricoxib, a selective COX-2 inhibitor, is a nonsteroidal anti-inflammatory drug (NSAID) that has showed comparable efficacy in acute and chronic pain, with fewer gastrointestinal (GI) adverse events compared with traditional NSAIDs. Therefore, we conducted a phase II randomized clinical trial to investigate whether etoricoxib could prevent or ameliorate the incidence and/or severity of docetaxel-induced acute pain syndrome. We also aimed to determine if there are any improvement of the late-onset peripheral neuropathy as well as quality of life with prophylactic etoricoxib for breast cancer patients who receive docetaxel chemotherapy.

Official Title
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Prevention of Taxane-associated Acute Pain Syndrome With Etoricoxib for Breast Cancer Patients: A Phase II Randomized Trial

Conditions
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Pain Syndrome

Intervention / Treatment
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* Drug: Etoricoxib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Age ≥18 years Stage I-III breast cancer ECOG 0-2 Received docetaxel-containing chemotherapy Exclusion Criteria: Existed any chronic pain or peripheral neuropathy Prior history of gastrointestinal bleeding or ulcer Long-term history of receiving oral corticoids, nonsteroid anti-inflammatory drugs (NSAIDs) or anti-histamines Allergies to NSAIDs or aspirin Blood creatinine level exceeds 1.5 times of the upper limit of normal range

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Etoricoxib<br>Prophylactic etoricoxib (60 mg) was administered orally at each course of docetaxel-containing chemotherapy, which started from the day of chemotherapy and was performed once per day for 8 days (day 1-8). | Drug: Etoricoxib<br>* Etoricoxib 60 Mg Oral Tablet<br>|
| No Intervention: Control<br>No prophylactic regimen was given. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall incidence of taxane-associated acute pain syndrome across all cycles of chemotherapy | Total incidence of myalgia and arthralgia of patients across all cycles of docetaxel chemotherapy | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence of taxane-associated acute pain syndrome at each cycle | Incidence of myalgia and arthralgia of patients at each cycle of docetaxel chemotherapy | 6 months | 
| severity of taxane-associated acute pain syndrome at each cycle | Severity of myalgia and arthralgia of patients at each cycle of docetaxel chemotherapy; the severity of pain was evaluated on a scale of 0 (no pain) to 10 (pain as bad as you can imagine). | 6 months | 
| duration of taxane-associated acute pain syndrome at each cycle | Duration of myalgia and arthralgia of patients at each cycle of docetaxel chemotherapy; the duration of pain was counted by days. | 6 months | 
| incidence of severe taxane-associated acute pain syndrome by cycle and across all cycles | incidence of severe myalgia and arthralgia (score, defined as greater than 5 on a scale from 0 to 10) of patients during the period of docetaxel chemotherapy by cycle and across all cycles | 6 months | 
| Functional Assessment of Cancer Therapy-Breast (FACT-B) subscale at each cycle | Functional Assessment of Cancer Therapy-Breast（FACT-B）subscale during the period of docetaxel chemotherapy was assessed; the scores range from 0 to 144, higher scores mean a better outcome (higher quality of life) | 6 months | 
| incidence of peripheral neuropathy after all cycles of chemotherapy | Functional Assessment of Cancer Treatment Neurotoxicity (FACT-Ntx) subscale (FACT-Ntx score <44), Eastern Cooperative Oncology Group neuropathy scale (ENS) subscale and EMG were performed at 3 months after the completion of chemotherapy. | 6 months | 
| adverse events | Assessment of adverse events was based on the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grading scale. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer, Docetaxel, Etoricoxib, Acute pain syndrome, Peripheral neuropathy