The Polyanalgesic Consensus Conference (PACC)®: Intrathecal Drug Delivery Guidance on Safety and Therapy Optimization When Treating Chronic Noncancer Pain.

INTRODUCTION: The International Neuromodulation Society convened a multispecialty group of physicians and scientists based on expertise with international representation to establish evidence-based guidance on intrathecal drug delivery in treating chronic pain. This Polyanalgesic Consensus Conference (PACC)® project, created more than two decades ago, intends to provide evidence-based guidance for important safety and efficacy issues surrounding intrathecal drug delivery and its impact on the practice of neuromodulation. MATERIALS AND METHODS: Authors were chosen on the basis of their clinical expertise, familiarity with the peer-reviewed literature, research productivity, and contributions to the neuromodulation literature. Section leaders supervised literature searches of MEDLINE, BioMed Central, Current Contents Connect, Embase, International Pharmaceutical Abstracts, Web of Science, Google Scholar, and PubMed from 2017 (when PACC® last published guidelines) to the present. Identified studies were graded using the United States Preventive Services Task Force criteria for evidence and certainty of net benefit. Recommendations are based on the strength of evidence or consensus when evidence is scant. RESULTS: The PACC® examined the published literature and established evidence- and consensus-based recommendations to guide best practices. Additional guidance will occur as new evidence is developed in future iterations of this process. CONCLUSIONS: The PACC® recommends best practices regarding intrathecal drug delivery to improve safety and efficacy. The evidence- and consensus-based recommendations should be used as a guide to assist decision-making when clinically appropriate.

Physicochemical Stability Study of the Morphine-Bupivacaine-Ziconotide Association.

OBJECTIVE: The aim of this study was to investigate the physicochemical stability of morphine-bupivacaine-ziconotide mixtures used in intrathecal analgesia in polypropylene syringes and intrathecal pumps. MATERIALS AND METHODS: The stability study method was conceived according to International Council for Harmonisation guidelines. For propylene syringes, six different mixtures of morphine-bupivacaine and ziconotide were assessed over seven days. Two storage temperatures were tested (5 °C ± 3 °C and 25 °C ± 2 °C). For implantable pumps, nine different mixtures were assessed over 60 days and stored at 37 °C. Assays were performed using ultrahigh-pressure liquid chromatography. Turbidity and pH also were measured throughout the study. RESULTS: Results confirmed excellent physicochemical stability for morphine and bupivacaine in the study for all conditions investigated (pumps at 37 °C, polypropylene syringes at 5 °C ± 3 °C and 25 °C ± 2 °C). Concerning ziconotide, after seven days, our study showed that every 95% confidence interval calculated had lower bounds >90% for all mixtures stored in polypropylene syringes. In implantable pumps, a decrease of the concentration was observed in all the mixtures studied. Moreover, the appearance of a degradation product confirmed the ziconotide degradation. CONCLUSION: All results are in favor with a physicochemical stable preparation for six mixture profiles when stored in polypropylene syringes at 5 °C ± 3 °C and 25 °C ± 2 °C. For mixtures stored in implantable pumps, the efficacy should decrease over time owing to the degradation of ziconotide. A trade-off between high morphine concentration and increased refill interval will need to be found by clinicians.

Intrathecal cervical analgesia for cancer pain: a 12-year follow-up study in a comprehensive cancer center.

BACKGROUND: Intrathecal analgesia plays a key role for patients suffering refractory cancer pain. Nevertheless, intrathecal drug delivery systems (IDDS), requiring a cervical catheter tip implantation, have been poorly described in medical literature. AIMS: A monocentric retrospective follow-up study was designed to evaluate results of cervical IDDS for cancer pain. PATIENTS AND METHODS: From January 2010 to December 2022, all intrathecal-treated patients were prescribed a combined intrathecal analgesics regimen through a catheter placed in the cervical vertebral canal. Post-implant assessment of pain was determined using a numeric rating scale (NRS). Patients were followed via day-hospital visits and telephone calls at least monthly. Pain scores were compared using the Wilcoxon's signed rank test. RESULTS: Ninety-eight patients were included in this study; all received intrathecal treatments. Implanted patients suffered from severe pain (mean presurgical maximum numerical rating score 8.02±0.24 despite a mean 562.56±127.72 mg of oral morphine equivalent daily dose). Mean survival time after intrathecal treatment start was 208.48±67 days. Intrathecal drug delivery systems provided pain relief compared with initial pain score with a significant statistical difference after 1 week, 1 month, 2 and 3 months (p<0.01). A 50% reduction in initial pain level was achieved in 93% of cases during the first week of intrathecal implant. CONCLUSIONS: Results suggest that long-term intrathecal treatment using a multidrug regimen for cancer-related pain through cervical intrathecal catheters was suitable and safe in our study population. We demonstrated a clinically and statistically significant pain reduction in patients using mainly a percutaneous lumbar approach.

Intrathecal Catheter for Chemotherapy in Leptomeningeal Carcinomatosis From HER2-Negative Metastatic Breast Cancer.

PURPOSE: Most oncological treatments for leptomeningeal metastasis (LM) do not cross the blood-brain barrier (BBB). One therapeutic option is intrathecal (IT) chemotherapy. Both the brain-implanted Omaya reservoir and lumbar puncture (LP) are classic routes for IT chemotherapy delivery. An intrathecal catheter (IC) connected to a subcutaneous port is a recently developed option for the management of chemotherapy infusions. It is essential to evaluate the efficacy and safety of chemotherapy infusion using such device. METHODS: We conducted a retrospective monocentric study within Institut de cancerologie de l'Ouest at Angers, including all patients with advanced breast cancer (aBC) with LM implanted with an IT device for IT chemotherapy between January 2013 and May 2020. The primary endpoint was overall survival (OS) and secondary endpoints included surgical feasibility, patient safety, and progression-free survival (PFS). The catheter was inserted through an LP, the tip was positioned at the right level and connected to a subcutaneous port implanted under the skin of the anterior thoracic wall. IT chemotherapy is painless and easy for qualified nurses to administer on an outpatient basis. RESULTS: Thirty women underwent the implantation. No failures occurred during the procedure. A total of 77% of patients reported no complications after implantation. Only three complications required surgical treatment. The median number of IT chemotherapy courses per patient was 8 (range, 2-27). The tolerance profile for iterative IT chemotherapy was manageable in ambulatory care. With a median follow-up of 76.5 months (95% confidence interval [CI], 11.6-not available), the median OS was 158 days (95% CI, 87-235), and the median PFS was 116 days (95% CI, 58-174). CONCLUSION: Infusing chemotherapy using an implanted catheter is an efficient option for managing IT chemotherapy with a good tolerance profile. Patient-reported outcomes for the evaluation of IT chemotherapy toxicity are currently being developed.

Correction: Bienfait et al. Evaluation of 8% Capsaicin Patches in Chemotherapy-Induced Peripheral Neuropathy: A Retrospective Study in a Comprehensive Cancer Center. Cancers 2023, 15, 349.

In the original publication [...].

Evaluation of 8% Capsaicin Patches in Chemotherapy-Induced Peripheral Neuropathy: A Retrospective Study in a Comprehensive Cancer Center.

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is often painful and can arise during or after the end of oncological treatments. They are mostly induced by platinum salts, taxanes, and immunotherapies. Their incidence is estimated between 19 and 85%. They can require a chemotherapy dose reduction or early termination. The European Society for Medical Oncology (ESMO) recommends high-concentration capsaicin patch (HCCP) in second line for the treatment of painful CIPN. This treatment induces a significative pain relief but only shown by low-powered studies. The objective of this study was to evaluate efficacy and tolerability of HCCP applications in CIPN. Methods: This monocentric observational retrospective real-world-data study of the CERCAN cohort took place in the Western Cancer Institute's Anaesthesiology and Pain Department at Angers, France. Independent pain physicians completed the CGIC (Clinician Global Impression of Change) for each patient who benefited from HCCP applications for painful CIPN starting from 1 January 2014 to 22 December 2021, based on the collected data after every patch application. Results: A total of 57 patients (80.7% women) was treated with HCCP for painful CIPN, and 184 applications were realized, consisting of 296 sessions. CGIC found an important or complete pain relief for 61 applications (33.2%, corresponding to 43.9% patients). We found less efficacy for platinum-salts-induced CIPN compared to others (p = 0.0238). The efficacy was significatively higher for repeated applications when HCCP was used in second line compared to third line (p = 0.018). The efficacy of HCCP was significatively higher starting the third application (p = 0.0334). HCCPs were mainly responsible for local adverse events found in 66.6% patients (65.1% burning or painful sensation, 21.1% erythema). Conclusion: HCCP applications in painful CIPN induce an important pain relief with a global satisfying tolerability.

Stability of Morphine Sulfate-Clonidine and Sufentanil-Clonidine Mixtures.

BACKGROUND: Spinal analgesia is recommended for intractable cancer pain. Morphine-clonidine and sufentanil-clonidine are often used in association in intrathecal drug delivery systems, injected by intraabdominal pumps. To refill these pumps and to limit patient transport, it may be necessary to ship the mixtures in polypropylene syringes to peripheral establishments located near patient homes. The purpose of this study is to determine the stability of morphine-clonidine and sufentanil-clonidine mixtures in polypropylene syringes to ensure the best and safest transport conditions and in implantable pumps for intrathecal use. MATERIALS AND METHODS: The stability study method was conceived according to the International Council for Harmonization guidelines. For polypropylene syringes, four different mixtures of morphine-clonidine and sufentanil-clonidine were assessed over seven days. Two storage temperatures were tested (5 ± 3 °C and 25 ± 2 °C). For implantable pumps, two different mixtures of morphine-clonidine and sufentanil-clonidine were assessed over 28 days and stored at 37 °C. RESULTS: For the morphine-clonidine mixtures in polypropylene syringes, all mixtures remained stable for five days in both storage conditions (5 ± 3 °C and 25 ± 2 °C) because of relative concentrations systematically positioned between 90% and 110% (95% CIs of the mean of three samples). The two mixtures in implantable pumps remained stable for 28 days. For the sufentanil-clonidine mixtures in polypropylene syringes, cold conservation kept all the preparations stable for seven days, whereas a quick degradation was observed after only two days for ambient storage conditions. This result is similar to that with an implantable pump, in which the concentration is <90% on day 7 for low concentration mixtures. No visual modification, no significant pH modification, and no changes in turbidity assays were observed in either study. CONCLUSION: This study shows the stability of the morphine-clonidine mixtures in syringes stored at 5 °C for five days and in implantable pumps stored at 37 °C for 28 days. For the sufentanil-clonidine mixtures, the results show stability in syringes for seven days at 5 °C. Pump results show stability of seven days for low concentrations and 28 days for high concentrations.

Ziconotide for the Management of Cancer Pain: A Budget Impact Analysis.

OBJECTIVES: Recent recommendations on starting dose, smaller dose increments, and longer intervals between dose increase have the potential to increase the safety of ziconotide administration in addition to improving its value for money. Ziconotide is not routinely commissioned in England, with one of the concerns being whether it represents the best use of resources. The aim of this project is to conduct a budget impact analysis to estimate the costs or savings associated with the changes in ziconotide dosage in addition to its use in combination with morphine for the management of cancer pain. MATERIALS AND METHODS: An open, Markov-like cohort decision analytic model was developed to estimate the budget impact of ziconotide in combination with morphine (ziconotide combination therapy) vs morphine monotherapy through intrathecal drug delivery (ITDD) for the management of cancer pain. The perspective adopted was that of the UK National Health Service, with a five-year time horizon. Sensitivity analyses were conducted to evaluate different scenarios. RESULTS: Ziconotide combination therapy was more expensive than treatment with morphine monotherapy. The total costs of ziconotide combination therapy and morphine monotherapy for the first year were £395,748 and £136,628 respectively. The estimated five-year cumulative budget impact of treatment with ziconotide combination therapy for the five-year time horizon was £2,487,539, whereas that of morphine monotherapy was £913,804. The additional costs in any of the first five years are below the resource impact significance level of £1 million for medical technologies in England. CONCLUSIONS: The results of this budget impact analysis suggest that although a combination of intrathecal ziconotide in combination with morphine is associated with higher costs to the health care system in England, the incremental costs are not significant. Routine commissioning of ziconotide alone or in combination with morphine would provide an alternative for a population with limited ITDD treatment options.

Management of Cancer-Related Pain With Intrathecal Drug Delivery: A Systematic Review and Meta-Analysis of Clinical Studies.

BACKGROUND: Despite increased attention paid to assessment and management, pain continues to be a prevalent and undertreated symptom in patients with cancer. Intrathecal drug delivery (IDD) is a therapeutic option that allows targeted delivery of analgesics to the intrathecal space. OBJECTIVE: The aim of this review was to examine the efficacy of managing cancer-related pain with IDD. Secondary objectives included the effects of IDD on systemic opioid use and infection rates. EVIDENCE REVIEW: A systematic search of the literature published between 1990 and 2019 was performed to identify studies evaluating the efficacy and/or safety of IDD with external or implanted pumps in patients with cancer-related pain. Data were extracted and meta-analyses performed to determine the mean changes in pain levels at short-, mid-, and long-term intervals; changes in opioid (oral morphine equivalent [OME]) daily dose; and infection rates. Changes were assessed compared with baseline. FINDINGS: Pain levels were decreased from baseline: On a 0 to 10 scale, mean differences were -4.34 (95% CI [-4.93 to -3.75], p < 0.001) at 4 to 5 weeks; -4.34 (95% CI [-5.07 to -3.62], p < 0.001) at 6 to 12 weeks; and -3.32 (95% CI [-4.60 to -2.04], p < 0.001) at >6 months. Weighted mean OME consumption was reduced by 308.24 (SE = 22.72) mg/d. Weighted mean infection rates were ∼3% for external and implanted pumps. CONCLUSIONS: Meta-analyses show a statistically significant and sustained decrease in cancer pain with IDD, compared with baseline. Systemic opioid consumption was reduced on average by >50% after IDD. Infection rates were comparable with other indications.

Physicochemical Stability Study of the Morphine-Ropivacaine-Ziconotide Association in Implantable Pumps for Intrathecal Administration.

PURPOSE: This study aimed to investigate the physicochemical stability of morphine-ropivacaine-ziconotide mixtures used in intrathecal analgesia. MATERIALS AND METHODS: Eight mixtures were studied to assess their stability profiles according to the initial drug concentrations used. The solutions obtained were put in implantable pumps and stored at 37 °C over a period of 60 days. Assays were performed using ultra high-pressure liquid chromatography. Turbidity and pH were also measured throughout the study. RESULTS: Results confirmed excellent physicochemical stability for morphine and ropivacaine. Concerning ziconotide, three of the eight mixtures did not show any sign of chemical instability: average concentrations remained constant throughout the 60 days. A decrease of the concentration was observed for the five other mixtures. Moreover, the appearance of a degradation product linked to oxidation confirmed the ziconotide degradation. CONCLUSIONS: All these results are in favor of a physicochemical stable preparation for three of the mixture profiles when stored in implantable pumps at 37 °C up to 60 days. For the five others, the efficacy should decrease over time owing to the degradation of ziconotide. The decrease in kinetics of the ziconotide concentration depends on the mixing profile. One possibility is to adapt the filling intervals according to the profile of the mixture. Finally, the results show the period of stability ensuring maximum analgesic efficacy for the eight mixture profiles studied.

Postoperative prophylactic intermittent noninvasive ventilation versus usual postoperative care for patients at high risk of pulmonary complications: a multicentre randomised trial.

BACKGROUND: Pulmonary complications are an important cause of morbidity and mortality after surgery. We evaluated the clinical effectiveness of noninvasive ventilation (NIV) in preventing postoperative acute respiratory failure. METHODS: This is an open, multicentre randomised trial that included patients at high risk of postoperative pulmonary complications after elective or semi-urgent surgery with an Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) score ≥45. Patients were randomly assigned to intermittent prophylactic face-mask NIV for 6-8 h day-1 or usual postoperative care. The primary outcome was in-hospital acute respiratory failure within 7 days after surgery. Patients who underwent surgery and postoperative extubation were included in the modified intended-to-treat analysis. Results are presented as n (%) and odds ratios (ORs) with 95% confidence intervals. RESULTS: Between November 2017 and October 2019, 266 patients were randomised and 253 included in the main analysis. Of these, 203 (80.2%) were male with a mean age of 68 (11) yr and an ARISCAT score of 53 (6); 237 subjects (93.7%) underwent cardiac or thoracic surgery. There were 125 patients allocated to prophylactic NIV and 128 to usual care. Unplanned treatment termination occurred in 58 subjects in the NIV group, which was linked to NIV discomfort for 36 subjects. There was no difference in the incidence of the primary outcome of postoperative acute respiratory failure between treatment groups (NIV: 30 of 125 subjects [24.0%] vs usual care: 35 of 128 subjects [27.3%]; OR 0.97 [0.90-1.04]; P=0.54). CONCLUSIONS: Prophylactic NIV was difficult to implement after high-risk surgery because of low patient compliance. Prophylactic NIV did not prevent acute respiratory failure. CLINICAL TRIAL REGISTRATION: NCT03629431 and EudraCT 2017-001011-36.

Effectiveness and Safety of Intrathecal Drug Delivery Systems for the Management of Cancer Pain: A Systematic Review and Meta-Analysis.

OBJECTIVES: Intrathecal drug delivery systems (IDDS) and spinal cord stimulation (SCS) have been proposed and assessed for the management of cancer pain; however, such treatments remain underused. We conducted a systematic review to evaluate the effectiveness and safety of IDDS and SCS for cancer pain. MATERIALS AND METHODS: Electronic databases MEDLINE, CENTRAL, EMBASE, and WikiStim were searched from 1988 to March 2021. Randomized controlled trials and observational studies of adults with pain related to cancer or its treatment who received an implantable IDDS or SCS were eligible for inclusion. The primary outcome of the review was change in pain intensity from baseline to the last available follow-up, measured using a visual analog scale or numerical rating scale. The protocol for this review is registered on PROSPERO (CRD42021240717). RESULTS: A total of 22 studies (24 reports) included a total of 3043 participants who received either IDDS or SCS for cancer pain. Eight studies reporting data for 405 participants with an IDDS could be included in the meta-analysis of pain intensity that showed a statistically significant reduction at the latest posttreatment follow-up time compared with baseline (mean difference [MD], -3.31; 95% CI, -4.18 to -2.45; p < 0.001). Six studies reporting data for 325 participants with an IDDS could be included in the meta-analysis of pain intensity that showed a statistically significant reduction up to one month after treatment compared with baseline (MD, -3.53; 95% CI, -4.06 to -3.00; p < 0.001). A meta-analysis including studies of participants with either an IDDS or an SCS device showed similar results. Improvements in other outcomes following implantation of IDDS also were observed. Postdural puncture headache was the most reported complication, whereas urinary retention, nausea, and vomiting were commonly reported side effects. CONCLUSION: Our findings suggest that IDDS is effective in reducing pain intensity for patients with cancer pain when compared with pretreatment.

Controversies in intrathecal drug delivery for cancer pain.

Pain and suffering related to cancer are challenging issues that continue to deserve consideration for treatment optimization. Advances in analgesic management and control of the underlying cancer have improved symptom management, yet many patients still suffer from uncontrolled pain. Intrathecal drug delivery has an established role in the management of refractory cancer pain, but there are significant knowledge gaps in our understanding and application of this therapy. This review addresses several areas of controversy, including the importance of intrathecal catheter tip location, the necessity of an intrathecal trial and the role of intrathecal ziconotide and local anesthetics. In each area, the evidence is discussed, with an emphasis on presenting practical clinical guidance and highlighting deficiencies in our knowledge that are worthy of future investigation.

Diagnosis, management and impact on patients' lives of cancer-related neuropathic pain (CRNP): A European survey.

OBJECTIVE: This study assessed the impact of cancer-related neuropathic pain (CRNP) on patients and the importance of the patient-healthcare professional (HCP) relationship in diagnosis and management. METHODS: A quantitative online survey was conducted involving adult patients from 13 European countries who had been diagnosed with treatable cancer and experienced symptoms of peripheral neuropathy. RESULTS: Of 24,733 screened respondents, 549 eligible persons met the inclusion criteria and completed the questionnaire. Among individuals still experiencing pain, 75% rated it as 'severe' or 'moderate'. In addition, 61% reported a negative impact on day-to-day activities, and 30% said they had stopped working as a result. A third of respondents had received no diagnosis of CRNP despite reporting painful symptoms to an HCP. HCPs spending enough time discussing pain and understanding the impact on patients' lives were each associated with an increased likelihood of a formal CRNP diagnosis. Compared with individuals currently in active cancer treatment, cancer survivors were less likely to have a diagnosis of CRNP or regular pain conversations with HCPs. CONCLUSION: CRNP remains under-recognised despite its substantial impact on patients' lives. Clinical practice may be improved by strengthening patient-HCP relationships around pain discussions and increasing the focus on pain management among cancer survivors.

Rationale and Recent Advances in Targeted Drug Delivery for Cancer Pain: Is It Time to Change the Paradigm?

BACKGROUND: Cancer pain prevalence remains high with more than 60% of patients with advanced cancer experiencing cancer-related pain. The undertreatment of pain due to concerns of opioid dependence or diversion, as well as the potential effect of opioids on tumor neogenesis, add to the suffering among cancer populations. OBJECTIVES: The aim of this narrative review was to assess evidence on the effectiveness, safety, cost-effectiveness, and advances of Intrathecal (IT) Drug Delivery Systems (IDDS) for the management of cancer pain. STUDY DESIGN: The present review was performed by searching for articles indexed in PubMed, MEDLINE, SciELO, Google Scholar, and Scopus. METHODS: Studies were included if they investigated patients with chronic cancer-related pain treated with IDDS and assessed experienced pain. We performed a narrative synthesis. RESULTS: IDDS have demonstrated efficacy in relieving cancer pain even in the challenging treatment of head and neck cancer pain. IDDS is also associated with a large reduction in serum opioid concentrations limiting adverse effects. When combined with other analgesics commonly used in the spinal space, but not systemically, pain relief may be dramatically improved. Advances in IT drug diffusion, including mixtures created with pharmaceutical compounding, improve the safety and accuracy of this therapy. IDDS is cost-effective and safe yet remains underutilized in this patient population. LIMITATIONS: Despite numerous clinical studies, only a small number of randomized trials have been conducted to evaluate the effectiveness of IDDS for cancer pain. CONCLUSIONS: This article presents an overview of the current state of evidence on the effectiveness, safety, cost-effectiveness, and advances of IDDS for the management of cancer pain. Despite current evidence, IDDS remains underutilized for people with cancer pain. Potential areas to facilitate its use are discussed. A shift in the paradigm of cancer pain treatment should be considered given the undertreatment rate, lack of benefits, and considerable risks associated with oral opioid medication in many patients who suffer from chronic cancer pain.

A Prospective, Real-World, Multinational Study of Naloxegol for Patients with Cancer Pain Diagnosed with Opioid-Induced Constipation-The NACASY Study.

The Naloxegol Cancer Study (NACASY) was a multinational European study aimed to evaluate the 4-week safety and efficacy of naloxegol in a real-world setting in patients with cancer pain diagnosed with opioid-induced constipation. The primary safety endpoint was the incidence of adverse events leading to study discontinuation. We recruited 170 patients who received at least one dose of naloxegol (i.e., safety population). Out of 170 patients, 20 (11.8%, 95%CI 6.9-16.6) discontinued the study due to adverse events, and, of them, 12 (7.1%, 95%CI 3.2-10.9%) were study discontinuations due to naloxegol-related adverse events. From 76 patients subjects who had completed both 4 weeks of treatment and 28 days of the diary, 55 patients (72.4%, 95% CI 62.3-82.4%) were regarded as responders (i.e., showed ≥3 bowel-movements per week and an increase of ≥1 bowel-movement over baseline) to naloxegol treatment. The Patient Assessment of Constipation-Quality of Life Questionnaire total score and all its subscales improved from baseline to 4 weeks of follow up. Our findings support and provide new evidence about the beneficial effect of naloxegol in terms of improvement of constipation and quality-of-life in patients with cancer-related pain and opioid-induced constipation and show a safety profile consistent with previous pivotal and real-world studies.

Peripheral Neuropathic Pain Following Breast Cancer: Effectiveness and Tolerability of High-Concentration Capsaicin Patch.

PURPOSE: Data supporting the use of high-concentration capsaicin patches (HCCPs) in breast cancer (BC) patients and BC survivors (BCSs) with peripheral neuropathic pain (PNP) are limited. This observational study evaluated the effectiveness and safety of HCCP applications in BCSs/BC patients with PNP. PATIENTS AND METHODS: Data from all patients treated with HCCP in the pain department of a French comprehensive cancer centre were collected from 01-Jan-2014 to 14-Oct-2020. Independent pain specialists completed the Clinical Global Impression of Change (CGIC) for each included patient based on data extracted from patient's electronic medical record compiled by the treating pain specialist after each HCCP application. RESULTS: Patients (N=279; mean age: 59.2 years; previous history of PNP medication: 54.5%) received on average 4.1 repeated HCCP applications (1141 HCCP applications); 68.8% received HCCP as an add-on to systemic therapy and 27.9% as first-line therapy. PNP was most frequently caused by surgery (62.4%) followed by chemotherapy (11.8%) and radiotherapy (6.5%). A complete or important analgesic effect was reported at least once by 82.3% of patients. A 6.0% reported no effect at all. For post-surgical PNP existing for <12 months and >10 years an important or complete effect was observed for 70.7% and 56.0% of applications. For chemotherapy- or radiotherapy-induced PNP, this important or complete effect was observed for 52.7% and 52.3% of applications, respectively. HCCP application was associated with site reactions in 54.4% of patients (mainly burning sensation or pain, 45.9%, or erythema, 30.8%) and high blood pressure in 7.2%. CONCLUSION: This real-world chart review provides important effectiveness and safety information to clinicians when considering topical options to treat PNP in BCSs/BC patients.

Cancer Pain Management-A European Perspective.

Cancer pain management is a major challenge in both Europe and the United States. Recent studies show that the incidence of cancer pain remains high and even increases at an advanced stage of the disease.