Abstract
Background: Cancer is the second leading cause of death globally. Up to 86% of advanced cancer patients experience significant pain, while 10-20% live in chronic pain. Besides, increasing prescription of opioids resulted in 33,000 deaths in the US in 2015. Both reduce patients' functional status and quality of life. While cancer survival rates are increasing, therapeutic options for chronic opioid refractory pain are still limited. Esketamine is the s-enantiomer of ketamine, with superior analgesic effect and less psychotomimetic side effects. Intranasal esketamine was approved by the FDA for treatment-resistant depression. However, its use in chronic cancer pain has never been tested. Therefore, we propose a phase II, randomized, placebo-controlled trial to evaluate the efficacy and safety of intranasal esketamine in chronic opioid refractory cancer pain. Methods and analysis: We will recruit 120 subjects with chronic opioid refractory pain, defined as pain lasting more than 3 months despite optimal therapy with high dose opioids (>60 mg morphine equivalent dose/day) and optimal adjuvant therapy. Subjects will be randomized into two groups: intranasal esketamine (56mg) and placebo. Treatment will be administered twice a week for four consecutive weeks. The primary outcome is defined as reduction in the Numeric Pain Rating Scale (NPRS) after first application. Secondary outcomes include NPRS reduction after four weeks, the number of daily morphine rescue doses, functional status and satisfaction, and depression. Conclusion: This study may extend therapeutic options in patients with chronic pain, thus improving their quality of life and reducing opioid use. Trial registration: Clinical Trials.gov, NCT04666623. Registered on 14 December 2020.
Highlights
Refractory pain is a challenging condition in Oncology
The primary aim is to investigate the analgesic efficacy of intranasal esketamine as an add-on therapy to potentially improve opioid resistant pain in cancer patients
Evaluation if esketamine treatment reduces the number of morphine rescues required daily by the patient
Summary
Refractory pain is a challenging condition in Oncology. More than half of the patients with advanced stage cancer experienced pain[1,2,3] and about 10 to 20% of the pain in cancer is refractory[4]. Ketamine was discovered in 1980, described as a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptor causing the inhibition of excitatory glutamate receptors in the central nervous system[5] It is commonly used as a general anesthetic agent, administered by intravenous or intramuscular route, but other usage and routes for this drug are being studied. One of the ketamine enantiomers largely studied nowadays for other potential use is esketamine, the most effective optical isomer of ketamine[3] The advantage of this enantiomer is that it induces less dissociative effects and more powerful analgesia and anesthesia[10]. A large randomized controlled trial is needed to prove that this drug is effective to relieve pain, is safe, and causes a reduction in opioid consumption. States and many other countries and efforts are strongly directed to combat it[17]
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