Adhesive capsaicin 8% patch for improved control of pain caused by chemotherapy-induced peripheral neuropathy in patients with multiple myeloma: A single-centre, seven-case series.

BACKGROUND: Capsaicin is a highly selective agonist of the transient receptor potential vanilloid 1. The adhesive capsaicin patch provides a high capsaicin concentration (8%) directly in the painful area - its efficacy in benign peripheral neuropathic pain (diabetic neuropathy or postherpetic neuralgia) has recently been described in the literature. However, there is scant evidence of its efficacy in chemotherapy-induced peripheral neuropathy (CIPN). This is a concern for patients with multiple myeloma, who suffer from peripheral neuropathic pain induced by first-line treatments (bortezomib or thalidomide). AIM: To describe improved control of CIPN in patients with multiple myeloma using adhesive capsaicin 8% patch. METHODS: We opted for a retrospective observational case series. Between October 2017 and October 2020, we collected clinical data from adult multiple myeloma patients affected by CIPN who were administered the capsaicin 8% patch in our palliative care outpatient clinic. We compiled Numerical Pain Rating Scale (NPRS) scores, patients' medication needs and performance status before and after patch application. RESULTS: Two women and five men with an average age of 62.85 years received bortezomib. Two patients (28.57% of the sample) also received thalidomide. The average NPRS score before patch application was 6.42/10. Five of the seven patients (71.42%) received a mean daily oral morphine dose of 52.85 mg/day, five (71.42%) received gabapentinoids and one (14.28%) received antidepressants. The average NPRS score decreased to 4/10 seven days after patch application, while the mean daily oral morphine dose remained stable. Performance status improved slightly in two patients (28.57%) and remained stable in the rest. One patient (14.28%) required an extra analgesic dose during patch application. CONCLUSIONS: Capsaicin 8% patch application appears to reduce pain intensity in patients with multiple myeloma suffering from CIPN.

Evidence on the analgesic role of bisphosphonates and denosumab in the treatment of pain due to bone metastases: A systematic review within the European Association for Palliative Care guidelines project.

BACKGROUND: Bisphosphonates and denosumab are well-established therapies to reduce the frequency and severity of skeletal-related events in patients with bone metastasis. However, the analgesic effect of these medications on bone pain is uncertain. AIM: To identify, critically appraise and synthesize existing evidence to answer the following questions: 'In adult patients with metastatic bone pain, what is the evidence that bisphosphonates and denosumab are effective and safe in controlling pain?' and 'What is the most appropriate schedule of bisphosphonate/denosumab administration to control bone pain?'. This review also updates the 2002 Cochrane review 'Bisphosphonates for the relief of pain secondary to bone metastases'. DESIGN: Standard systematic review and narrative synthesis. DATA SOURCES: MEDLINE, EMBASE and Cochrane CENTRAL databases were searched for relevant articles published through 31 January 2014. A manual search was also performed. Study inclusion criteria were: a) conducted in adult patients; b) randomized controlled trial or meta-analisys; c) reported efficacy of bisphosphonates or denosumab on pain and/or decribed side effects versus placebo or other bisphosphonate; and d) English language. RESULTS: The database search yielded 1585 studies, of which 43 (enrolling 8595 and 7590 patients, respectively, in bisphosphonate and denosumab trials) met the inclusion criteria. Twenty-two (79%) of the 28 placebo-controlled trials found no analgesic benefit for bisphosphonates. None of the denosumab studies assessed direct pain relief. CONCLUSION: Evidence to support an analgesic role for bisphosphonates and denosumab is weak. Bisphosphonates and denosumab appear to be beneficial in preventing pain by delaying the onset of bone pain rather than by producing an analgesic effect per se.

Efficacy and Safety of Methadone as a Second-Line Opioid for Cancer Pain in an Outpatient Clinic: A Prospective Open-Label Study.

INTRODUCTION: Most clinical reports on methadone rotation describe outcomes in hospitalized patients. The few studies that have included outpatients are retrospective. The aim of this study was to assess the efficacy and safety of methadone as a second-line opioid in adult patients with advanced cancer after rotation in routine clinical practice at a palliative care outpatient clinic. PATIENTS AND METHODS: This was a prospective, open-label study of 145 patients whose treatment was rotated from other opioids to methadone. Informed consent was obtained in all cases. The main outcome measure was change in the variable "worst pain" at day 28. Pain and pain interference were assessed with the Brief Pain Inventory, with side effects evaluated according to the Common Terminology Criteria for Adverse Events version 3.0. Pain levels were evaluated at study entry and at days 3, 7, 9, 14, 21, and 28. RESULTS: Rotation to methadone was performed for the following reasons: poor pain control (77.9%), opioid side effects (2.1%), or both (20%). The mean daily oral morphine equivalent dose before rotation was 193.7 mg. The median worst and average pain scores decreased significantly (p < .0001) from baseline to day 28: The median worst pain score decreased from 9 (interquartile range [IQR]: 8-10) to 6 (IQR: 3-8), and the median average pain score decreased from 6 (IQR: 5-7) to 4 (IQR: 2-5). The proportions of patients with moderate to severe worst and average pain decreased by 30.3% and 47.5%, respectively, by day 28. No increase in opioid toxicity was observed during the study. CONCLUSION: In outpatients with advanced cancer, rotation to methadone as a second-line opioid was efficacious and safe when using a tiered scheme with close follow-up by experienced health professionals. IMPLICATIONS FOR PRACTICE: The results of this study, conducted prospectively under real clinical conditions, support the efficacy and safety of oral methadone as a second-line opioid in ambulatory patients with cancer. Moreover, these findings corroborate previously reported outcomes in retrospective outpatient studies and prospective studies that evaluated inpatient populations. Although more research into methadone rotation strategies is still needed, this study describes a successful tiered scheme of oral methadone rotation that was proven safe and effective during follow-up.

Antitumoral Agent-Induced Constipation: A Systematic Review.

BACKGROUND: Constipation is a common symptom in patients receiving antitumoral treatment. The mechanisms underlying antitumoral agent-induced constipation (ATAIC) are poorly defined. This systematic review aimed to analyze and synthesize the available information related to the prevalence, etiology, and treatment of ATAIC. METHODS: A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines was conducted. The review included human studies written in English, French, or Spanish involving patients with cancer and containing information about the prevalence, etiology, and treatment of ATAIC. RESULTS: A total of 73 articles were included. The reported prevalence ranged from 0.8% to 86.6%. Six studies reported an ATAIC prevalence of over 50%. The prevalence rates of constipation of grades 3 and 4 ranged between 0 and 11%. The importance of enteric neuronal integrity in gastrointestinal function was reported. The articles with the highest levels of evidence in relation to ATAIC treatment obtained in this systematic review studied treatments with acupuncture, sweet potato, osteopath, probiotics, and moxibustion. CONCLUSIONS: The prevalence of constipation in patients undergoing antitumoral treatment is very diverse. Studies specifically designed to report the prevalence of antineoplastic treatment-induced constipation are needed. The importance of enteric neuronal integrity in gastrointestinal function was described. Thus, neuroprotection could be an area of research for the treatment of chemotherapy-induced gastrointestinal disorders.

Switching Ratio from Parenteral to Oral Methadone 1:1.2 Is Safer Compared with Ratio 1:2 in Patients with Controlled Cancer Pain: A Multicenter Randomized-Controlled Trial (RATIOMTD-010810).

Background: The most commonly used switching ratio from parenteral to oral methadone is 1:2. Methadone is highly bioavailable and a lower ratio might result in similar analgesia with less toxicity. Objective: To compare success and side effects with two ratios from parenteral to oral methadone: 1:2 versus 1:1.2 in hospitalized patients with cancer pain. Design: A multicenter double-blind randomized clinical trial. Settings/Particiants: Inpatients with well-controlled cancer pain with parenteral methadone requiring rotation to the oral route. Measurements: Outcomes included pain intensity (Brief Inventory Pain), opioid toxicity (Common Toxicology Criteria for Adverse Events), and methadone dose. Success was defined as no toxicity with good pain control at 72 hours. Results: Thirty-nine of forty-four randomized patients were evaluable: 21 in ratio 1:2 and 18 in ratio 1:1.2. Seventy-one percent male. Median age 65 years. No significant differences in basal clinical characteristics between both groups. Median methadone dose pre/post switching was 24.5 mg ±13.5 and 49 mg ±27.3 for ratio 1:2, versus 23.3 mg ±9.4 (p: not significant) and 28 mg ±11.3 (p < 0.01) for ratio 1:1.2. Pain was well controlled without differences between both ratios. Drowsiness at day +1 (p < 0.017) and myoclonus at day +3 (p < 0.019) were more prevalent in group 1:2. Success was observed in 12 patients in ratio 1:2 versus 18 in ratio 1:1.2 (p < 0.001). Methadone side effects were observed in 12 patients in ratio 1:2 (mainly neurotoxicity symptoms) versus 2 in ratio 1:1.2 (p < 0.005). Conclusion: Ratio 1:1.2 when changing from parenteral to oral methadone resulted in lower toxicity and no difference in analgesia. More conservative dose adjustment during methadone route change should be considered. European Clinical Trials Register (EudraCT No. 2010-024092-39).