Prevention of Taxane-associated Acute Pain Syndrome With Etoricoxib

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

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.

Study Overview

• Status: Completed
• Conditions: Pain Syndrome
• Intervention / Treatment: Drug: Etoricoxib

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 144
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Guangdong General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Etoricoxib; 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; Etoricoxib 60 Mg Oral Tablet
No Intervention: Control; No prophylactic regimen was given.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Guangdong Provincial People's Hospital
• Investigators: Principal Investigator: Kun Wang, MD, Guangdong Provincial People's Hospital

Publications and helpful links

General Publications

• Zhang J, Gao HF, Yang C, Zhu T, Ji F, Yang M, Zhang L, Li J, Cheng M, Zhang T, Shen B, Chen Y, Wang K. Prevention of taxane-associated acute pain syndrome with etoricoxib for patients with breast cancer: A phase II randomised trial. Eur J Cancer. 2022 Aug;171:150-160. doi: 10.1016/j.ejca.2022.05.019. Epub 2022 Jun 17.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2020
• Primary Completion (Actual): April 22, 2021
• Study Completion (Actual): June 28, 2021

Study Registration Dates

• First Submitted: September 13, 2020
• First Submitted That Met QC Criteria: September 21, 2020
• First Posted (Actual): September 25, 2020

Study Record Updates

• Last Update Posted (Actual): February 14, 2022
• Last Update Submitted That Met QC Criteria: January 29, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Docetaxel; Breast Cancer; Peripheral neuropathy; Etoricoxib; Acute pain syndrome
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Pain; Neurologic Manifestations; Disease; Syndrome; Somatoform Disorders; Acute Pain; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Cyclooxygenase 2 Inhibitors; Etoricoxib
• Other Study ID Numbers: 20190516

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No