Opioid therapy vs. multimodal analgesia in head and neck Cancer (OPTIMAL-HN): study protocol for a randomized clinical trial

Abstract

Background Radiation-induced mucositis (RIM) pain confers substantial morbidity for head and neck cancer (HNC) patients undergoing radiotherapy alone (RT) or chemoradiotherapy (CRT), often reducing treatment compliance. However, no standard currently exists for the treatment of RIM, and high dose opioid therapy, with its associated side effects and increased risk for chronic opioid use, remains the cornerstone of HNC pain management. The goal of this randomized clinical trial is to compare multimodal analgesia using analgesic medications with different mechanisms of action, to the institutional standard of opioid analgesia alone, in order to ascertain the optimal analgesic regimen for the management of RIM pain in HNC patients. Methods In this open-label, single-institution, non-inferiority, randomized clinical trial, sixty-two patients with mucosal head and neck malignancies treated with curative-intent radiation will be randomized in a 1:1 ratio, stratified by RT or CRT, between Arm 1: opioid analgesia alone as per the institutional standard, or Arm 2: multimodal analgesia using Pregabalin, Acetaminophen, and Naproxen, in addition to opioids, if required. The primary endpoint is the average 11-Numeric Rating Scale (11-NRS) score for pain during the last week of radiation treatment. Secondary endpoints include: average weekly opioid use, duration of opioid requirement, average daily 11-NRS score for pain, average weekly opioids dispensed, quality of life, hospitalizations for analgesic medication-induced complications, time to feeding tube insertion, weight loss, toxicity, treatment interruptions, and death within 3 months of completing RT treatment. Patients are eligible once analgesia is required for moderate 4/10 pain. Discussion This study will assess the efficacy and safety of multimodal analgesia and its impact on opioid requirements, clinical outcomes, and quality of life, as a potential new standard treatment for RIM pain in HNC patients undergoing definitive RT or CRT. Trial registration ClinicalTrials.gov Identifier: NCT04221165. Date of registration: January 9, 2020. Appendix 2 reports the World Health Organization trial registration dataset.

Principles of Specific Treatment and Palliative Care in Advanced Head and Neck Cancer

“…After some studies have been undergone, it seems that multimodal analgesic therapy may become the now gold standard in the treatment of pain caused by radiotherapy-induced mucositis. This implies the association between NSAIDs + acetaminophen + pregabalin +/-opioid [26].…”

Sociodemographic Differences in Patient-Reported Pain and Pain Management of Patients With Head and Neck Cancer in a Community Oncology Setting

“…Pain reporting mechanisms are subjective and often lack standardization; this is especially true in the management of HNC, in which pain is a significant part of symptom burden and opioid use is a mainstay for pain management. 13,27,28 Given that these patients are vulnerable to the stressors associated with both the disease and its management, it is especially important to examine prevalent characteristics in the group of patients with HNC who report pain, as well as pain management for these patients. We found that while there was no significant difference between the number of pain incidents reported by White patients with HNC and non-White patients with HNC, White patients were significantly more likely to receive new pain medications; reported time to pain resolution was also longer for White patients than for non-White patients.…”