Topical Ketamine with Other Adjuvants: Underutilized for Refractory Cancer Pain? A Case Series and Suggested Revision of the World Health Organization Stepladder for Cancer Pain

Abstract

Background: Uncontrolled cancer pain is a significant problem in palliative medicine. Opioids are often firstline treatment that increase risks of analgesic tolerance and hyperalgesia. Topical ketamine with other adjuvant pain medications is an often-overlooked treatment, yet may be most effective in difficult-to-treat cancer pain. Objective: We report a case series of hospice patients with uncontrolled cancer pain who were suboptimally treated with opioids and nerve blocks, whose symptoms responded to topical ketamine with other adjuvants. We review the pronociceptive properties of opioids and how topical multimodal treatment of cancer pain can be more effective than standard opioids, other topical adjuvant medications, and nerve blocks. We discuss the shortcomings of the World Health Organization (WHO) stepladder for the treatment of cancer pain and suggest an adjuvant treatment algorithm, directing physicians to appropriate adjuvant pain agents based on pain type and distinct receptor actions. Design: This is a retrospective case series of patients who responded to topical multimodal pain treatment with implementation of findings into an addendum to the WHO stepladder. Subjects: Subjects were from a case series of community-based hospice patients with previously uncontrolled cancer pain. Measurement: Measurement was made by self-report of pain levels using the 10-point numeric pain rating scale. Results: Patients' pain was controlled with topical adjuvant medications with return to previously lost function and prevention of otherwise escalating opioid dosing. Conclusions: These patient cases reveal how ketamine-based topical treatment for cancer pain can be more effective than standard opioids, other topical adjuvant medications, and nerve blocks with no noted side effects and observed reduction in opioid consumption.

Scoping Review of Off-Label Topical Analgesia in Palliative, Hospice and Cancer Care: Towards Flexibility in Evidence-Based Medicine

“…Scoping studies are “meant to ‘map’ relevant literature in a field of interest”. 6 , 8 Arksey and O’Malley 8 describe two “main differences between a systematic review and a scoping study”: “A systematic review might typically focus on a well-defined question where appropriate study designs can be identified in advance, whilst a scoping study tends to address broader topics where many different study designs might be applicable.” “The systematic review aims to provide answers to questions from a relatively narrow range of quality assessed studies, whilst a scoping study is less likely to seek to address very specific research questions nor consequently, to assess the quality of included studies.” …”

“… 5 However, regulatory or quasi-governmental, eg, WHO, guidance concerning topical agents for hospice, palliative and cancer care pain regimens is hampered by a dearth of randomized and blinded controlled studies. 6 A committee recently convened by the US National Academies of Science, Engineering and Medicine (NASEM) undertook a broad review of the use of topical medications for the treatment of pain. 7 Their recommendations (published in 2020) spanned standard treatments in patients with acute (eg, musculoskeletal) or chronic (eg, neuropathic or inflammatory) noncancer pain.…”

A review of the clinical applications of ketamine in pediatric oncology

“…The evaluation of topical ketamine preparations for chemotherapyinduced peripheral neuropathic pain has yielded variable results, with some suggesting a promising role but many studies indicating no significant benefit. [86][87][88] Topical ketamine is a safe and effective analgesic for decreasing posttonsillectomy pain in children, and has been used as a skin preparation for noncancer pain. 24,89,90 Preliminary evidence for ketamine mouthwash for oral mucositis pain had suggested a beneficial role in adults.…”

Ketamine in Pediatric Oncology: a drug review

“…The evaluation of topical ketamine preparations for chemotherapy-induced peripheral neuropathic pain has yielded variable results, with some suggesting a promising role but many studies indicating no significant benefit. 91,92,93 Topical ketamine is a safe and effective analgesic for decreasing post-tonsillectomy pain in children, and has been used as a skin preparation for non-cancer pain. 26,94,95 Preliminary evidence for ketamine mouthwash for oral mucositis pain had suggested a beneficial role in adults, but a recent RCT evaluating the role of ketamine mouthwash for oral mucositis pain relief in children (N=44; 8-18 years) found ketamine to be ineffective at a dose of 1 mg/kg.…”