ziconotide and Cancer-Pain

Targeted intrathecal (IT) drug delivery systems (IDDS) are well established as an effective treatment of patients with chronic nonmalignant or malignant pain, and as a tool for management of patients with severe spasticity. The risk to benefit ratio of IDD makes it a relatively safe therapy for both cancer- and noncancer-related pain, but it is not free of risks, so it should be managed at specific centers. Recent technological advances, new therapeutic applications, reported complications, and the costs as well as maintenance required for this therapy require the need to stay up to date about new recommendations that may improve outcomes. This chapter reviews all technological issues regarding IDDS implantation with follow-up and pharmacological recommendations published during recent years that provide evidence-based decision-making process in the management of chronic pain and spasticity in patients.

Topics: Analgesics, Non-Narcotic; Analgesics, Opioid; Baclofen; Cancer Pain; Chronic Pain; Drug Delivery Systems; GABA-B Receptor Agonists; Humans; Infusion Pumps, Implantable; Muscle Relaxants, Central; Muscle Spasticity; Neuroprotective Agents; omega-Conotoxins; Pain Management; Risk Factors

Intrathecal drug delivery systems (IDDS) for cancer pain remain little employed despite a high level of efficiency even though the technique is widely recommended. This review aims to summarize recent advances in IDDS for cancer patients.. The respective roles of catheter positioning, volume and flow rate in diffusion of intrathecal treatments, as well as the individual roles of blood pressure, heart rate, and amplitude of the respiratory movements in cerebrospinal fluid (CSF) treatment dispersion, are now well established. Models are available using MRI data. Morphine has long been the gold standard in first line treatment, but recent publications conclude that ziconotide has largely proven its efficiency and that adverse effects are controllable. Four recent publications have evaluated cohorts of cancer patients treated by IDDS in 315 patients. All found a great efficiency of intrathecal treatment for cancer pain. Technical innovations include new catheters and anchorage devices for easier placement and a lower rate of complication. Three-dimensional (3D) CT scan appears to be a noninvasive technique for the diagnosis of catheter complications. Ultrasound should be used to locate pump septum for refill.. All recent recommendations highlight the efficiency of IDDS and propose to use it sooner.

Topics: Analgesics, Non-Narcotic; Analgesics, Opioid; Betamethasone; Cancer Pain; Clinical Trials as Topic; Costs and Cost Analysis; Humans; Injections, Spinal; Morphine; omega-Conotoxins; Tomography, X-Ray Computed; Ultrasonography

Opioids are the primary choice for managing chronic cancer pain. However, many nonopioid therapies are currently prescribed for chronic cancer pain with little published evidence comparing their efficacy.. Electronic databases were searched for randomized controlled trials (RCTs) comparing any systemic pharmaceutical intervention and/or combination thereof in treating chronic cancer pain. The primary outcome was global efficacy reported as an odds ratio (OR). The secondary outcome was change in pain intensity reported as a standardized mean difference (SMD).. We included 81 RCTs consisting of 10,003 patients investigating 11 medication classes. Most RCTs (80%) displayed low risk of bias. The top-ranking classes for global efficacy were nonopioid analgesics (network OR, 0.30; 95% credibility interval [CrI], 0.13 to 0.67), nonsteroidal anti-inflammatory drugs (network OR, 0.44; 95% CrI, 0.22 to 0.90), and opioids (network OR, 0.49; 95% CrI, 0.27 to 0.86), whereas the top-ranked interventions were lidocaine (network OR, 0.04; 95% CrI, 0.01 to 0.18; surface under the cumulative ranking curve analysis [SUCRA] score, 98.1), codeine plus aspirin (network OR, 0.22; 95% CrI, 0.08 to 0.63; SUCRA score, 81.1), and pregabalin (network OR, 0.29; 95% CrI, 0.08 to 0.92; SUCRA score, 73.8). In terms of reducing pain intensity, we found that no class was superior to placebo, whereas the following top-ranked interventions were superior to placebo: ziconotide (network SMD, -24.98; 95% CrI, -32.62 to -17.35; SUCRA score, 99.8), dezocine (network SMD, -13.56; 95% CrI, -23.37 to -3.69; SUCRA score, 93.5), and diclofenac (network SMD, -11.22; 95% CrI, -15.91 to -5.80; SUCRA score, 92.9).. There are significant differences in efficacy among current regimens for chronic cancer pain. Our evidence suggests that certain nonopioid analgesics and nonsteroidal anti-inflammatory drugs can serve as effectively as opioids in managing chronic cancer pain.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Bayes Theorem; Bridged Bicyclo Compounds, Heterocyclic; Cancer Pain; Chronic Pain; Codeine; Comparative Effectiveness Research; Diclofenac; Female; Humans; Lidocaine; Male; Middle Aged; Neoplasms; Network Meta-Analysis; Odds Ratio; omega-Conotoxins; Pregabalin; Randomized Controlled Trials as Topic; Tetrahydronaphthalenes; Treatment Outcome; Young Adult

The purpose of the present investigation is to summarize the body and quality of evidence including the most recent studies in support of intrathecal drug delivery systems and spinal cord stimulation for the treatment of cancer-related pain.. In the past 3 years, a number of prospective studies have been published supporting intrathecal drug delivery systems for cancer pain. Additional investigation with adjuvants to morphine-based analgesia including dexmedetomidine and ziconotide support drug-induced benefits of patient-controlled intrathecal analgesia. A study has also been recently published regarding cost-savings for intrathecal drug delivery system compared to pharmacologic management, but an analysis in the Ontario, Canada healthcare system projects additional financial costs. Finally, the Polyanalgesic Consensus Committee has updated its recommendations regarding clinical guidelines for intrathecal drug delivery systems to include new information on dosing, trialing, safety, and systemic opioid reduction. There is still a paucity of clinical evidence for spinal cord stimulation in the treatment of cancer pain. There are new intrathecal drugs under investigation including various conopeptides and AYX1. Large, prospective, modern, randomized controlled studies are still needed to support the use of both intrathecal drug delivery systems as well as spinal cord stimulation for cancer pain populations. There are multiple prospective and small randomized controlled studies that highlight a potential promising future for these interventional modalities. Related to the challenge and urgency of cancer pain, the pain practitioner community is moving toward a multimodal approach that includes discussions regarding the role of intrathecal therapies and spinal cord stimulation to the individualized treatment of patients.

Topics: Analgesia, Patient-Controlled; Analgesics, Non-Narcotic; Cancer Pain; Dexmedetomidine; Evidence-Based Medicine; Humans; Infusion Pumps, Implantable; omega-Conotoxins; Pain Management; Prospective Studies; Spinal Cord Stimulation

The present study discusses the utilization of neuraxial drug delivery (NDD) for the management of cancer pain, based on recent trials, reviews, and guidelines with a focus on cost analysis.. Almost all recent publications suggest that more stringent research is needed to improve evidence on NDD, particularly as conflicting reports exist regarding cost effectiveness of drug delivery systems. The combination of local anesthetics and opioids, with or without clonidine, continues to be reported as beneficial with the utilization of patient controlled systems providing an advantage over continuous ones. Interestingly, the use of opioids as an adjunct to local anesthetics may not enhance analgesia but the addition of dexamethasone is useful for incident cancer-related bone pain. Ziconitide remains supported as first-line therapy in districts where it is available - United States and Europe. Although new targeted drugs are being designed for cancer pain management, none have seen human clinical trials in the last year.. The ability to demonstrate cost effectiveness of NDD is variable from region to region. Less expensive externalized systems may pose a viable alternative. With the exception of dexamethasone, no new drugs have been shown to provide any benefit to conventional medications.

Topics: Cancer Pain; Cost-Benefit Analysis; Dexamethasone; Drug Delivery Systems; Humans; omega-Conotoxins

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.. 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.. 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.. 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.

Topics: Analgesics, Non-Narcotic; Cancer Pain; Humans; Injections, Spinal; Morphine; Neoplasms; omega-Conotoxins; State Medicine

Topics: Analgesics, Non-Narcotic; Cancer Pain; Humans; Injections, Spinal; Neoplasms; omega-Conotoxins