Treatment Of Chronic Cancer Pain Research Articles

Discovering a combination of natural compounds for treatment of chronic cancer pain based on bioinformatics

Background & Objective: The incidence of malignant disease has been increasing the world over, and with it the number of patients suffering from severe cancer pain is also increasing with every passing day. We aimed to find a potentially effective combination of natural compounds for the treatment of chronic cancer pain (CCP) using bioinformatics methods, and provide a theoretical basis for subsequent laboratory experiments and clinical trials.
 Methodology: Six natural compounds, including bakuchiol, cinnamaldehyde, curcumin, eugenol, salicin and xanthoxylin, were selected as candidates for new drugs by consulting a large number of relevant literatures. Their targets were obtained from the Swiss Target Prediction database. The related targets of CCP were obtained from GeneCards, OMIM and DisGent databases. Cytoscape software was used to construct the "compound-target-disease" network. Protein-protein interaction network (PPI) was constructed by STRING platform; GO function and KEGG pathway enrichment analysis were performed by R language software.
 Results: A total of 197 targets were obtained from the Swiss Target Prediction database; 10767 CCP of disease targets were obtained after searching and removing duplications in the disease database. Twelve core targets, AKT1, SRC, STAT3, ESR1, RELA, EP300, MAPK1, MAPK14, CCNA2, EGFR, GSK3B and PRKCZ, were identified by PPI analysis. GO functional enrichment analysis yielded 1950 entries. KEGG enrichment analysis revealed 134 pathways with statistical significance, among which pathways related to CCP were more than those related to nerve.
 Conclusion: The mechanism of action of these six compounds in the treatment of chronic cancer pain is multi-target and multi-pathway related. Through protein-protein interaction analysis, GO function and KEGG pathway enrichment analysis, it is found that these six compounds can be used as candidate drugs for the treatment of chronic cancer pain, which will be further studied in the future.
 Key words: Bioinformatics; Natural Compounds; Chronic Cancer Pain; New Drug Discovery
 Citation: Si W. Discovering a combination of natural compounds for treatment of chronic cancer pain based on bioinformatics. Anaesth. pain intensive care 2023;27(5):431−439; DOI: 10.35975/apic.v27i5.2293
 Received: February 21, 2023; Reviewed: March 06, 2023; Accepted: April 28, 2023

A clinical case of the use of a new selective μ1-opioid analgesic Tafalgin in the treatment of chronic cancer pain

In the Russian Federation, tetrapeptide tyrosyl-D-arginyl-phenylalanyl-glycine amide (Tafalgin), a novel analgesic, selective agonist of 1-opioid receptors, was developed and approved in 2022. The article presents the first experience of the successful use of Tafalgin in treating chronic pain in a cancer patient with poor tolerance to traditional opioids (tramadol, tapentadol, morphine). At baseline, pain severity, according to the Neurological Rating Scale (NRS), was 57 points at rest and up to 9 points in motion out of the maximum 10. The combination of 400 mg/day of tramadol with gabapentin and a non-steroidal anti-inflammatory drug was ineffective; 400 mg/day of tapentadol in combination with gabapentin and a non-steroidal anti-inflammatory drug also was ineffective. Morphine tablets 60 mg/day were effective (NRS score of 23), but unrelenting nausea and vomiting were unmanageable and significantly reduced quality of life. Reducing the dose of oral morphine to 20 mg/day mitigated adverse events but reduced the effectiveness of pain relief (resting NRS score of 4 points). Tafalgin 4 mg subcutaneously BID, then TID reduced the pain severity to an average daily NRS score of 1.22 over the first 3 days of treatment with no adverse events. Sleep, appetite, and physical activity improved. The patient received Tafalgin for 84 days, and she gained 5 kg due to improved nutrition during that time. The drug is comparable in efficacy to morphine and is associated with fewer adverse events. A limitation to widespread use is the availability of a formulation for subcutaneous injection only.

Non-pharmacological integrative therapies for chronic cancer pain

Chronic pain is one of the most detrimental symptoms exhibited by cancer patients, being an indication for opioid therapy in up to half of the patients' receiving chemotherapy and in 90% of advanced cases. Various successful non-pharmacological integrative therapy options have been explored and implemented to improve the quality of life in these patients. This review aims to highlight the mechanisms implicated; assessment tools used for cancer pain and summarize current evidence on non-pharmacological approaches in the treatment of chronic cancer pain. A review of the literature was conducted using a combination of MeSH keywords including "Chronic cancer pain," "Assessment," "Non-pharmacological management," and "Integrative therapy." Data on the approach and assessment of chronic cancer pain as well as non-pharmacological integrative options have been displayed with the help of figures and tables. Of note, non-pharmacological integrative management was divided into three subcategories; physical therapy (involving exercise, acupuncture, massage, and transcutaneous electric nerve stimulation), psychosocial therapy (e.g. mindful practices, supportive therapy), and herbal supplementation. The use of non-pharmacological integrative therapy in the management of chronic cancer pain has been grossly underestimated and must be considered before or as an adjuvant of other treatment regimens to ensure appropriate care.

The combined analgesic effect of pregabalin and morphine in the treatment of pancreatic cancer pain, a retrospective study.

BackgroundPregabalin is commonly used to relieve neuropathic pain. However, data are lacking on its efficacy for the treatment of chronic cancer pain. The purpose of this study was to determine the analgesic efficacy of pregabalin combined with morphine in the management of pancreatic cancer pain.MethodsThis study reviewed patients who were prescribed morphine and 150 mg/d pregabalin between 1 January 2017 and 10 November 2018 in our institute. The primary outcomes of this study were the average pain score and dose of morphine. Secondary outcomes included characters of breakthrough cancer pain, functional interference related to pain, anxiety/depression status, and incidence of treatment‐related adverse events during the study.ResultsA total of 240 patients with pain related to pancreatic cancer were included in the study. The results showed that patients of both combination therapy group (pregabalin+morphine) and monotherapy group (morphine) achieved similar analgesic efficacy, demonstrated by NRS (2.4 ± 0.9 vs. 2.6 ± 0.9; combination vs. monotherapy) at the end of the study. Mean daily dose of morphine used in the combination group was significant lower compared to monotherapy group (39.5 ± 16.0 mg vs. 61.5 ± 19.3 mg, net difference 23.5, 95% CI: 18.4–28.6, p < 0.001). The change of functional interference score related to pain was significantly different between combination and monotherapy group (12.0 ± 0.4 vs. 9.8 ± 4.9; net difference, 2.3; 95% CI: 1.1–3.3; p < 0.001). Patients in combination therapy group had experienced shorter duration of breakthrough cancer pain than those in monotherapy group (X2 p < 0.001, Cramer's V:0.36). The incidence of somnolence, dizziness, and cognitive dysfunction were significantly higher in the combination group compared to monotherapy group. No serious treatment‐related side effects were observed.ConclusionsThe findings of this study supported the use of pregabalin with morphine to relieve pain in patients of pancreatic cancer.

The possibilities of using xenon therapy in patients with severe cancer pain

In accordance with the clinical recommendations of the World Health Organization and the Ministry of Health of the Russian Federation, the main analgesics for the treatment of chronic cancer pain are non-opioid and opioid analgesics, given stepwise in combination with co-analgesics and adjuvant drugs. As a rule, this stepwise scheme of painkilling is effective in most cases. However, 20-30% of patients cannot achieve an acceptable level of pain relief despite the use of these analgesics in combination. Is there another way to help such patients? Interventional methods of analgesia are an option, yet not all patients agree to invasive methods due to the possible side effects and unavailability of these methods. In these cases other mechanisms of analgesia are required, such as NMDA receptor antagonists, which reduce opioid tolerance and hyperalgesia. Still not all the drugs of this group can be applied in our practice. Analgesic properties of nitrous oxide can only be found in high anesthetic doses. Another option is metadon, but it is forbidden and cannot be used in our country. Still one more option is ketamine, which has severe side effects. In our clinical practice we decided to use xenon, which has NMDA inhibition effects. Its analgesic effect and safety have been confirmed in numerous studies. This publication aims to demonstrate a successful clinical case when we used xenon and oxygen inhalations course for the treatment of a severe cancer pain with a patient who had been taking morphine by mouth.

Are strong opioids equally effective and safe in the treatment of chronic cancer pain? A multicenter randomized phase IV ‘real life’ trial on the variability of response to opioids

Guidelines tend to consider morphine and morphine-like opioids comparable and interchangeable in the treatment of chronic cancer pain, but individual responses can vary. This study compared the analgesic efficacy, changes of therapy and safety profile over time of four strong opioids given for cancer pain. In this four-arm multicenter, randomized, comparative, of superiority, phase IV trial, oncological patients with moderate to severe pain requiring WHO step III opioids were randomly assigned to receive oral morphine or oxycodone or transdermal fentanyl or buprenorphine for 28 days. At each visit, pain intensity, modifications of therapy and adverse drug reactions (ADRs) were recorded. The primary efficacy end point was the proportion of nonresponders, meaning patients with worse or unchanged average pain intensity (API) between the first and last visit, measured on a 0-10 numerical rating scale. (NCT01809106). Forty-four centers participated in the trial and recruited 520 patients. Worst pain intensity and API decreased over 4 weeks with no significant differences between drugs. Nonresponders ranged from 11.5% (morphine) to 14.4% (buprenorphine). Appreciable changes were made in the treatment schedules over time. Each group required increases in the daily dose, from 32.7% (morphine) to 121.2% (transdermal fentanyl). Patients requiring adjuvant analgesics ranged from 68.9% (morphine) to 81.6% (oxycodone), switches varied from 22.1% (morphine) to 12% (oxycodone), discontinuation of treatment from 27% ( morphine) to 14.5% (fentanyl). ADRs were similar except for effects on the nervous system, which significantly prevailed with morphine. The main findings were the similarity in pain control, response rates and main adverse reactions among opioids. Changes in therapy schedules were notable over time. A considerable proportion of patients were nonresponders or poor responders. NCT01809106 (https://clinicaltrials.gov/ct2/show/NCT01809106?term=cerp&rank=2).

Potential economic impact on hospitalisations of the Palliative Care Clinical Studies Collaborative (PaCCSC) ketamine randomised controlled trial.

The aim of the present study was to estimate the potential healthcare cost savings associated with reduced prescribing of subcutaneous ketamine for the treatment of chronic cancer pain after publication of the Palliative Care Clinical Studies Collaborative (PaCCSC) ketamine randomised controlled trial (RCT), to provide further reasons to modify ketamine prescribing practice in this setting. Potential cost savings in this setting were estimated from a health system perspective using a 1-year impact model. The model was populated with estimates derived using an epidemiological approach informed by morbidity and prevalence data, the PaCCSC feasibility study, ketamine RCT and national ketamine utilisation survey results, as well as clinical opinion. The total estimated annual hospitalisation costs associated with subcutaneous ketamine prescribing were A$3 899 600 (2605 bed-days). A 17% reduction in ketamine prescribing lowered hospitalisation costs to A$3 236 668 (2162 bed-days), a reduction of A$662 932 (443 bed-days) because of reduced in-patient stays associated with ketamine toxicity and prescribing process. The findings from the modelled impact analysis suggest that dissemination of the PaCCSC ketamine RCT results may have saved the Australian healthcare system approximately A$663 000 in annual hospitalisation costs and freed up 443 in-patient bed-days, although there was high uncertainty within the study. Wider dissemination over time and targeted, local de-adoption strategies could result in further savings.

The role of ketamine in the treatment of chronic cancer pain.

Background and aimKetamine is a drug used for the induction and maintenance of general anesthesia, for the treatment of postoperative and posttraumatic acute pain, and more recently, for the reduction of postoperative opioid requirements. The main mechanism of action of ketamine is the antagonization of N-methyl-D-aspartate (NMDA) receptors that are associated with central sensitization. In the pathogenesis of chronic pain and particularly in neuropathic pain, an important role is played by the activation of NMDA receptors. Although ketamine is indicated and used for the treatment of chronic cancer pain as an adjuvant to opioids, there are few clinical studies that clearly demonstrate the effectiveness of ketamine in this type of pain.The aim of this study is to analyze evidence-based clinical data on the effectiveness and safety of ketamine administration in the treatment of chronic neoplastic pain, and to summarize the evidence-based recommendations for the use of ketamine in the treatment of chronic cancer pain.MethodWe reviewed the literature from the electronic databases of MEDLINE, COCHRANE, PUBMED, MEDSCAPE (1998–2014), as well as chapters of specialized books (palliative care, pain management, anesthesia).ResultsA number of studies support the effectiveness of ketamine in the treatment of chronic cancer pain, one study does not evidence clear clinical benefits for the use of ketamine, and some studies included too few patients to be conclusive.ConclusionsKetamine represents an option for neoplasic pain that no longer responds to conventional opioid treatment, but this drug should be used with caution, and the development of potential side effects should be carefully monitored.

Efficacy and safety of a fixed combination of tramadol and paracetamol (acetaminophen) as pain therapy within palliative medicine.

Goal:The goal of the research was to determine the efficacy of a fixed combination of tramadol and paracetamol (acetaminophen) in the treatment of pain of patients with the advanced stage of cancer.Material and methods:A prospective study was conducted at the Center for Palliative Care, University Clinical Center Tuzla, Bosnia and Herzegovina, from January 1st to December 31st 2013. A total of 353 patients who were treated with a fixed combination of tramadol and acetaminophen (37.5 mg and 325 mg) at the initial dosage 3x1 tablet (112.5 mg tramadol and 975 mg acetaminophen) for pain intensity 4, up to 4x2 tablets (300 mg of tramadol and 2600 mg paracetamol) for pain intensity 7 and 8. If the patient during previous day has two or more pain episodes that required a “rescue dose” of tramadol, increased was the dose of fixed combination tramadol and acetaminophen to a maximum of 8 tablets daily (300 mg of tramadol and 2600 mg paracetamol). Statistical analysis was performed by biomedical software MedCalc for Windows version 9.4.2.0. The difference was considered significant for P<0.05.Results:The average duration of treatment with a fixed combination tramadol and acetaminophen was 57 days (13-330 days). Already after 24 hours of treatment the average pain score was significantly lower (p<0.0001) compared to the admission day [5.00 (4:00 to 8:00) during the first days versus 2.00 (1:00 to 7:00) during the second day of treatment]. The average dose of the fixed combination tramadol and acetaminophen tablets was 4.8 ± 1.8 (180 mg of tramadol and 1560 mg paracetamol). Side effects, in the treatment of pain with a fixed combination tramadol and acetaminophen, were found in 29.18% of patients, with a predominance of nausea and vomiting.Conclusion:Fixed combination of tramadol and acetaminophen can be used as an effective combination in the treatment of chronic cancer pain, with frequent dose evaluation and mild side effects.

Catechol-o-methyltransferase polymorphisms predict opioid consumption in postoperative pain.

Previous studies have associated the catechol-O-methyltransferase (COMT) enzyme rs4680 polymorphism with opioid consumption in the treatment of chronic cancer pain. In this study, we evaluated the association between COMT rs4680 and rs4818 polymorphisms and opioid consumption in the acute postoperative period after a nephrectomy. Opioid consumption and pain scores were evaluated in 152 patients for 48 hours after nephrectomy. The genotype of each patient was determined using polymerase chain reaction on DNA extracted from blood samples. The association between rs4680 and rs4818 genotypes and opioid consumption was evaluated using general linear model regression analysis. All P values and confidence intervals were Bonferroni corrected for the 3 comparisons among genotypes. In the 24-hour period after surgery (COMT rs4680), patients homozygous for the variant Val/Val consumed 36% (95% confidence interval, 31%-41%) more opioids than patients homozygous for the Met/Met group (P = 0.009). No statistically significant differences among the 3 genotype groups were noted for pain scores or emesis medication use in the first 24 hours after surgery. There was a statistically significant increase in emesis medication use in patients possessing the CC genotype of rs4818 when compared to patients carrying the GG genotypes (P = 0.035). In the 6- to 48-hour postsurgery period, there was significantly higher opioid consumption in the high-activity homozygotes Val/Val than in the homozygous Met/Met group for COMT rs4680 (0-6 h: P = 0.005; 0-12 h: P = 0.015; 0-24 h: P = 0.015; and 0-48 h: P = 0.023). Patients in the homozygous GG group COMT rs4818 single nucleotide polymorphism showed statistically significant differences in opioid consumption in the first 6 hours after nephrectomy compared with heterozygous CG patients (P = 0.02). The genetic variant of the COMT rs4680 single nucleotide polymorphism is associated with variability in opioid consumption in postoperative nephrectomy patients. The COMT rs4818 polymorphism may prove useful in predicting emesis medication use postoperatively.

Targeting putative mu opioid/metabotropic glutamate receptor-5 heteromers produces potent antinociception in a chronic murine bone cancer model

The therapeutic management of chronic pain associated with many cancers is problematic due to the development of tolerance and other adverse effects during the disease progression. Recently we reported on a bivalent ligand (MMG22) containing both mu agonist and mGluR5 antagonist pharmacophores that produced potent antinociception in mice with LPS-induced acute inflammatory pain via a putative MOR-mGluR5 heteromer. In the present study we have investigated the antinociception of MMG22 in a mouse model of bone cancer pain to determine its effectiveness in reducing this type of chronic nociception. There was a 572-fold increase in the potency of MMG22 over a period of 3–21 days that correlated with the progressive increase in hyperalgesia induced by bone tumor growth following implantation of fibrosarcoma cells in mice. The enhancement of antinociception with the progression of the cancer is possibly due to inhibition of NMDA receptor-mediated hyperalgesia via antagonism of mGluR5 and concomitant activation of MOR by the MMG22-occupied heteromer. Notably, MMG22 was 3.6-million-fold more potent than morphine at PID 21. Since MMG22 exhibited a 250,000-times greater potency than that of a mixture of the mu opioid (M19) agonist and mGluR5 antagonist (MG20) monovalent ligands, the data suggest that targeting the putative MOR-mGluR5 heteromer is far superior to univalent interaction with receptors in reducing tumor-induced nociception. In view of the high potency, long duration (>24h) of action and minimal side effects, MMG22 has the potential to be a superior pharmacological agent than morphine and other opiates in the treatment of chronic cancer pain and to serve as a novel pharmacologic tool.

Treatment of cancer pain: Spanish Society of Medical Oncology (SEOM) recommendations for clinical practice

Cancer pain should be controlled in most patients, however this is not always achieved. These guidelines describe the classification, evaluation and treatment of chronic cancer pain in accordance with the WHO treatment strategy of pain stages: mild, moderate and severe. For treatment during the third stage, we cover titration and rotation of opioids, as well as their side effects and prevention. Also described is neuropathic pain and refractory pain, coadjuvant treatments and non pharmacological analgesic treatments. Finally, treatment of breakthrough pain is defined.

The application of genomic and molecular data in the treatment of chronic cancer pain

Many cancer patients will develop complex pain syndromes requiring aggressive, innovative, and comprehensive multimodal pain management strategies. Recently, data from both animal studies and clinical trials have allowed clinical research to focus on creating applicable clinical treatment strategies. This article is a review of genomic and molecular data, which has contributed to creating novel modalities for use in clinical pain management of patients with cancer-induced pain.

Role of intranasal fentanyl in breakthrough pain management in cancer patients

Fentanyl is a strong opioid analgesic, which is commonly used in the form of a transdermal patch for the treatment of chronic cancer pain. An intranasal route of fentanyl administration is a novel treatment for breakthrough cancer pain (BTCP). The prevalence, assessment, and management of BTCP is outlined in this paper, and basic pharmacodynamic and pharmacokinetic properties, dosing guidelines, and clinical experience with the use of intranasal fentanyl in this indication are discussed. Intranasal fentanyl is an attractive and convenient mode of BTCP treatment in opioid-tolerant patients due to its quick onset and short duration of action, noninvasive administration route, high bioavailability, and avoidance of a hepatic first-pass effect. Until now, few clinical trials have been conducted with intranasal fentanyl, but all have confirmed its usefulness and acceptability in BTCP treatment. Intranasal fentanyl may be used in opioid-tolerant patients without nasal pathologies. The dose should be titrated in each patient regardless of the regular opioid dose administered. Future studies should compare intranasal fentanyl with other fentanyl formulations used for BTCP management, and with analgesia, adverse effects, and quality of life taken into consideration.

Role of intranasal fentanyl in breakthrough pain management in cancer patients

Role of intranasal fentanyl in breakthrough pain management in cancer patients Wojciech LeppertDepartment of Palliative Medicine, Poznan University of Medical Sciences, Poznan, PolandAbstract: Fentanyl is a strong opioid analgesic, which is commonly used in the form of a transdermal patch for the treatment of chronic cancer pain. An intranasal route of fentanyl administration is a novel treatment for breakthrough cancer pain (BTCP). The prevalence, assessment, and management of BTCP is outlined in this paper, and basic pharmacodynamic and pharmacokinetic properties, dosing guidelines, and clinical experience with the use of intranasal fentanyl in this indication are discussed. Intranasal fentanyl is an attractive and convenient mode of BTCP treatment in opioid-tolerant patients due to its quick onset and short duration of action, noninvasive administration route, high bioavailability, and avoidance of a hepatic first-pass effect. Until now, few clinical trials have been conducted with intranasal fentanyl, but all have confirmed its usefulness and acceptability in BTCP treatment. Intranasal fentanyl may be used in opioid-tolerant patients without nasal pathologies. The dose should be titrated in each patient regardless of the regular opioid dose administered. Future studies should compare intranasal fentanyl with other fentanyl formulations used for BTCP management, and with analgesia, adverse effects, and quality of life taken into consideration.Keywords: adverse effects, analgesia, breakthrough pain, intranasal fentanyl, opioid analgesics, treatment

Opioid misuse in oncology pain patients

The problem of therapeutic opioid misuse largely affects patients who need opioids to treat chronic pain conditions. Opioid misuse is rarely an overt clinical problem during end of life or acute pain treatment. Misuse attaches a stigma to opioid use, and makes many patients and prescribers reluctant to use these uniquely effective drugs, even when misuse is unlikely. Cancer was once an explosive, typically terminal disease and became the prototype for end-of-life opioid pain treatment. However, cancer is no longer such an explosive disease, and many cancer sufferers can now expect to have a prolonged, even normal, lifespan. They may need pain treatment, but this treatment should not be modeled on palliative care paradigms. This article describes the underlying mechanisms of opioid dependence and its progression to addiction, and suggests a cautious approach to opioid treatment of chronic cancer pain that aims to minimize the problem of misuse.

Transdermal fentanyl: an updated review of its pharmacological properties and therapeutic efficacy in chronic cancer pain control.

Fentanyl is a synthetic opioid agonist which interacts primarily with the mu-opioid receptor. The low molecular weight, high potency and lipid solubility of fentanyl make it suitable for delivery by the transdermal therapeutic system. These patches are designed to deliver fentanyl at a constant rate (25, 50, 75 and 100 microg/h), and require replacement every 3 days. Data from randomised, nonblind trials suggest that transdermal fentanyl is as effective as sustained-release oral morphine in the treatment of chronic cancer pain, as reported by patients using visual and numerical analogue scales as well as verbal description scales. No obvious differences in health-related quality of life were found in patients with chronic cancer pain when comparing transdermal fentanyl with sustained-release oral morphine. Nevertheless, significantly more patients expressed a preference for transdermal fentanyl than for sustained-release oral morphine after a randomised, nonblind, crossover trial. Because of the formation of a fentanyl depot in the skin tissue, serum fentanyl concentrations increase gradually following initial application, generally levelling off between 12 and 24 hours. Thereafter, they remain relatively constant, with some fluctuation, for the remainder of the 72-hour application period. Once achieved, steady-state plasma fentanyl concentrations can be maintained for as long as the patches are renewed. The most frequently observed adverse events during transdermal fentanyl administration (as with other opioid agonists) included vomiting, nausea and constipation. Data from a nonblind, randomised trials suggest that constipation occurs less frequently in patients receiving transdermal fentanyl than in those given sustained-release oral morphine. The most serious adverse event reported in US premarketing trials was hypoventilation, which occurred with an incidence of approximately 2%. Adverse reactions related to skin and appendages (i.e. rash and application site reactions - erythema, papules, itching and oedema) were reported in 153 patients with cancer at a frequency between 1 and 3%. Transdermal fentanyl is a useful opioid-agonist for the treatment of moderate to severe chronic cancer pain. The advantages of transdermal fentanyl include ease of administration and the 3-day application interval. These factors coupled with a lower incidence of constipation are likely to contribute to the reported patient preference of transdermal fentanyl over sustained-release oral morphine.

Transdermal Fentanyl in Opioid-Naive Cancer Pain Patients: An Open Trial Using Transdermal Fentanyl for the Treatment of Chronic Cancer Pain in Opioid-Naive Patients and a Group Using Codeine

To treat cancer pain, physicians often decide to jump directly from step 1 of the World Health Organization (WHO) analgesic ladder to step 3. The use of transdermal fentanyl in patients with cancer pain who had either used no opioid before, or only codeine, is evaluated in the present trial. Both opioid-naive ( N = 14) and codeine-using ( N = 14) patients started with transdermal fentanyl in the lowest available delivery rate (25 μg/hr). Immediate-release oral morphine was present as “rescue” medication. Transdermal fentanyl provided good to excellent pain relief in the majority (68 %) of these patients. During the study, 5 patients continued with 25 μg/hr, and the others used a higher dose. Clinically relevant respiratory depression was not observed. The common side effects of opioids were found; constipation was mentioned by 3 patients (11 %). Transdermal fentanyl appeared a safe analgesic in these opioid-naive cancer pain patients. In this study, WHO step 2 could be skipped without untoward complications.

A Patient Preference Study Comparing Two Extended-Release Morphine Sulfate Formulations (Once-Daily Kadian?? versus Twice-Daily MS Contin??) for Cancer Pain

Objective: To compare pain control, patient preference and tolerability for two extended-release ® capsules (administered once daily) and MS Contin® tablets (administered twice daily), in the treatment of chronic cancer pain.

Morphine or Oxycodone in Cancer Pain?

Oxycodone is an opioid analgesic that closely resembles morphine. Oxymorphone, the active metabolite of oxycodone, is formed in a reaction catalyzed by CYP2D6, which is under polymorphic genetic control. The role of oxymorphone in the analgesic effect of oxycodone is not yet clear. In this study, controlled-release (CR) oxycodone and morphine were examined in cancer pain. CR oxycodone and morphine were administered to 45 adult patients with stable pain for 3?6 days after open-label titration in a randomized, double-blind, cross-over trial. Twenty patients were evaluable. Both opioids provided adequate analgesia. The variation in plasma morphine concentrations was higher than that of oxycodone, consistent with the lower bioavailability of morphine. Liver dysfunction affected selectively either oxycodone or morphine metabolism. Three patients with markedly aberrant plasma opioid concentrations are presented. Significant individual variation in morphine and oxycodone metabolism may account for abnormal responses during treatment of chronic cancer pain.