ziconotide and Neoplasms

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

Targeted intrathecal (IT) drug delivery systems (IDDS) are an option in algorithms for the treatment of patients with moderate to severe chronic refractory pain when more conservative options fail. This therapy is well established and supported by several publications. It has shown efficacy and is an important tool for the treatment of spasticity, and both cancer and nonmalignant pain. 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, Opioid; Baclofen; Bupivacaine; Catheters, Indwelling; Chronic Pain; Clonidine; Drug Delivery Systems; Humans; Inflammation; Infusion Pumps, Implantable; Injections, Spinal; Neoplasms; omega-Conotoxins; Psychiatric Status Rating Scales; Spine

Intrathecal drug administration for the control of intractable pain has been practiced over many years in various countries; however, because of government regulation, no drugs except baclofen are approved for chronic intrathecal use in Japan. In this review, I have summarized the current international situation regarding the chronic intrathecal administration of various types of drugs for the control of intractable cancer and non-cancer pain. Morphine is the gold standard for this purpose, but its combination with local anesthetics or clonidine may be essential. Although this combination has presented strong evidence of cancer pain control, it shows weak evidence of non-malignant chronic pain control, probably because of the complex pathophysiology of the latter condition. A few new drugs such as ziconotide and gabapentin have been investigated, but the effective control of neuropathic pain, including complex regional pain syndrome, still appears difficult. Contrary to the general belief, intrathecal drug administration via an implantable pump is cost-effective, and I believe that this intrathecal drug delivery system should be used more extensively used for pain management in Japan.

Topics: Amines; Analgesics, Opioid; Anesthetics, Local; Baclofen; Calcium Channel Blockers; Clonidine; Cyclohexanecarboxylic Acids; Drug Therapy, Combination; GABA Agonists; Gabapentin; gamma-Aminobutyric Acid; Humans; Infusion Pumps, Implantable; Injections, Spinal; Morphine; Neoplasms; Neuralgia; omega-Conotoxins; Pain, Intractable

Ziconotide (formerly SNX-111) selectively blocks N-type voltage-sensitive calcium channels and may be effective in patients with pain that is refractory to opioid therapy or those with intolerable opioid-related adverse effects.. To assess the safety and efficacy of intrathecal ziconotide in patients with pain that is refractory to conventional treatment.. Double-blind, placebo-controlled, randomized trial conducted from March 12, 1996, to July 11, 1998, at 32 study centers in the United States, Australia, and the Netherlands. Patients were 111 individuals ages 24 to 85 years with cancer or AIDS and a mean Visual Analog Scale of Pain Intensity (VASPI) score of 50 mm or greater. Patients were randomly assigned in a 2:1 ratio to receive ziconotide or placebo treatment.. Intrathecal ziconotide was titrated over 5 to 6 days, followed by a 5-day maintenance phase for responders and crossover of nonresponders to the opposite treatment group.. Mean percentage change in VASPI score from baseline to the end of the initial titration period.. Of the evaluable population, 67 (98.5%) of 68 patients receiving ziconotide and 38 (95%) of 40 patients receiving placebo were taking opioids at baseline (median morphine equivalent dosage of 300 mg/d for the ziconotide group and 600 mg/d for the placebo group; P =.63, based on mean values), and 36 had used intrathecal morphine. Mean (SD) VASPI scores were 73.6 (1.8) mm in the ziconotide group and 77.9 (2.3) mm in the placebo group (P =.18). Mean VASPI scores improved 53.1% (95% confidence interval [CI], 44.0%-62.2%) in the ziconotide group and 18.1% (95% CI, 4.8%-31.4%) in the placebo group (P<.001), with no loss of efficacy of ziconotide in the maintenance phase. Pain relief was moderate to complete in 52.9% of patients in the ziconotide group compared with 17.5% in the placebo group (P<.001). Five patients receiving ziconotide achieved complete pain relief, and 50.0% of patients receiving ziconotide responded to therapy compared with 17.5% of those receiving placebo (P =.001).. Intrathecal ziconotide provided clinically and statistically significant analgesia in patients with pain from cancer or AIDS.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; Aged, 80 and over; Analgesics; Calcium Channel Blockers; Double-Blind Method; Female; Humans; Injections, Spinal; Male; Middle Aged; Neoplasms; omega-Conotoxins; Pain; Pain Measurement; Pain, Intractable

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

Topics: Abdominal Pain; Adrenal Cortex Hormones; Analgesia; Analgesics; Analgesics, Non-Narcotic; Anesthesia, Conduction; Anesthetics; Catheters, Indwelling; Chronic Pain; Complex Regional Pain Syndromes; Headache Disorders; Humans; Injections, Epidural; Injections, Spinal; Narcotics; Neoplasms; Nerve Block; omega-Conotoxins; Phantom Limb; Post-Dural Puncture Headache; Post-Traumatic Headache; Quality of Life; Syndrome; Trigeminal Neuralgia; Vascular Headaches

Ziconotide is a nonopioid intrathecal analgesic drug used to manage moderate to severe chronic pain. The aim of this work is to assess the safety and efficacy of intrathecal (IT) combination of ziconotide and morphine in malignant pain refractory to high doses of oral opioids. Patients with malignant pain refractory to high oral opioids doses with a mean visual analogue scale of pain intensity (VASPI) score of ≥ 70 mm were enrolled. An IT combination therapy was administered: Ziconotide was started at a dose of 2.4 μg/day, followed by increases of 1.2 μg/day at intervals of at least 7 days, and an initial IT daily dose of morphine was calculated based on its oral daily dose. Percentage change in VASPI scores from baseline was calculated at 2 days, at 7 days, and weekly until the first 28 days. The mean percentage change of VASPI score from baseline was used for efficacy assessment. Safety was monitored based on adverse events and routine laboratory values. Twenty patients were enrolled, with a mean daily VASPI score at rest of 90±7. All had a disseminated cancer with bone metastases involving the spine. The percentage changes in VASPI mean scores from baseline to 2 days, 7 days, and 28 days were 39±13% (95% confidence interval [CI]=13.61-64.49, P<.001), 51±12% (95% CI=27.56-74.56, P<.001), and 62±13% (95% CI=36.03-87.89%, P<.001), respectively. Four patients experienced mild adverse events related to the study drugs. In conclusion, an IT combination of low doses of ziconotide and morphine allows safe and rapid control of oral opioid-refractory malignant pain.

Topics: Adult; Aged; Aged, 80 and over; Analgesics, Non-Narcotic; Analgesics, Opioid; Drug Therapy, Combination; Female; Humans; Injections, Spinal; Male; Middle Aged; Morphine; Neoplasms; omega-Conotoxins; Pain Measurement; Pain, Intractable; Prospective Studies; Treatment Outcome

Topics: Analgesics, Non-Narcotic; Animals; HIV Infections; Humans; Injections, Spinal; Neoplasms; Neuralgia; omega-Conotoxins; Pain Measurement; Snails

Topics: Acquired Immunodeficiency Syndrome; Analgesics; Humans; Infusion Pumps; Injections, Spinal; Neoplasms; omega-Conotoxins; Pain, Intractable

Topics: Acquired Immunodeficiency Syndrome; Calcium Channel Blockers; Clinical Trials, Phase III as Topic; Humans; Neoplasms; omega-Conotoxins; Pain, Intractable; Peptides