Management Of Breakthrough Cancer Pain Research Articles

Budget impact analysis of the fentanyl buccal tablet for treatment of breakthrough cancer pain.

BackgroundThe purpose of this study was to assess the economic impact of the fentanyl buccal tablet for the management of breakthrough cancer pain (BTcP) in Spain.MethodsA 4-year budget impact model was developed for the period 2012–2015 for patients with BTcP from the perspective of the Spanish National Health System. BTcP products included in this model were rapid-onset opioids containing fentanyl (buccal, sublingual, or nasal transmucosal). Prevalence data on cancer, BTcP, opioid use, and number of BTcP episodes were obtained from the literature. Input data on health care resources associated with opioid use and opioid-induced side effects were obtained by consulting experts in oncology from different Spanish hospitals. Resources used included drugs, medical and emergency visits, other nonpharmacologic treatments, and treatment of opioid-induced side effects. Unit costs were obtained from the literature, and a 3% discount rate was applied to costs. Based on the unit costs for drugs and health care resources, the annual BTcP treatment costs per patient associated with each fentanyl product were determined to estimate the overall budget impact based on the total treatment population and the percentage of drug utilization associated with each product. One-way sensitivity analyses were conducted to test the robustness of the model.ResultsPatients treated with oral opioids for BTcP were estimated at 23,291 in 2012, with an increase up to 23,413 in 2015. The average annual budget savings, with an increase of fentanyl buccal tablets, fentanyl sublingual tablets, and intranasal fentanyl spray, and a decrease in oral transmucosal fentanyl citrate, was estimated at €2.6 million, which represents a 0.5% decrease in the total costs of BTcP over the next 4 years. Results of the sensitivity analysis showed that the model was most sensitive to drug cost per day for the fentanyl buccal tablet. A 50% decrease in the daily cost of the fentanyl buccal tablet resulted in the largest overall decrease in budget impact of €5.4 million.ConclusionThe increase in use of the fentanyl buccal tablet leads to overall savings in the budget impact for the Spanish National Health System. Although the economic impact of treatment for BTcP was shown to increase over 4 years due to population growth, the average annual cost per patient was reduced by €29 with increased use of the fentanyl buccal tablet.

The management of breakthrough cancer pain - educational needs a European nursing survey

Poorly managed cancer pain is well known to profoundly impact the patient's daily life and interfere with quality of life. Nurses who cared for patients with cancer from 12 European countries participated in a survey of breakthrough cancer pain practice. The purpose was to investigate how nurses assess breakthrough cancer pain, use of standardised tools, confidence in supporting patients and awareness of medications. Responses from 1241 participants showed country variations. The majority of the sample was female, Germany had the highest proportion of male nurses (21.0%), followed by Greece (15.8%). A significantly larger proportion of nurses with longer experience and more education (78.8%) used a comprehensive definition of breakthrough cancer pain. Significant variations in training were found; 71% of Finnish nurses had received training compared with 6% of Greek nurses. Training and using a standardised assessment tool was associated with a significant increase in the nurses' perceived ability to distinguish between breakthrough and background pain. Nurses in countries with the highest proportion of training were most confident in supporting patients. In conclusion, there still exists problems with effective management of patients' breakthrough cancer pain, continuing inability to define the difference between background and breakthrough cancer pain leads to poor treatment.

Single-dose fentanyl sublingual spray for breakthrough cancer pain

Breakthrough cancer pain (BTCP) is defined as a transient exacerbation of pain that arises in patients with otherwise controlled persistent pain. BTCP typically has a rapid onset and relatively short duration, but it causes a significant amount of physical and psychological distress for patients. Several rapid-onset fentanyl formulations have been introduced in the USA to replace traditional oral opioids for the treatment of BTCP: a transmucosal lozenge, a sublingual orally disintegrating tablet, a buccal tablet, a buccal soluble film, a pectin nasal spray and, the newest formulation to enter the market, a sublingual spray. This article reviews the six rapid-onset formulations of fentanyl approved in the USA for the management of BTCP with emphasis on describing the published literature on fentanyl sublingual spray. The different fentanyl formulations vary in pharmacokinetic properties and ease of use, but all have a rapid onset and a relatively short duration of analgesia. Fentanyl sublingual spray has demonstrated absorption within 5 minutes of administration, with fentanyl plasma concentrations increasing over the first 30 minutes and remaining elevated for 60–90 minutes in pharmacokinetic studies in healthy subjects. Fentanyl sublingual spray shows linear dose proportionality, and changes in the temperature or acidity of the oral cavity do not alter its pharmacokinetic properties. In patients with BTCP, statistically significant pain relief is measurable at 5 minutes after administration of fentanyl sublingual spray, when compared with placebo, with significant pain relief lasting at least 60 minutes after administration. Adverse events are typical of opioid treatment and are considered mild to moderate in intensity. In summary, fentanyl sublingual spray provides rapid onset of analgesia and is a tolerable and effective treatment for BTCP.

Management of Breakthrough Cancer Pain

Breakthrough cancer pain has been defined as a transitory increase in pain intensity that occurs despite relatively stable and adequately controlled background pain. More than half of cancer patients with chronic pain suffer by some form of breakthrough cancer pain. The management of breakthrough cancer pain is comprehensive and includes pharmacological and nonpharmacological approaches. The principal treatment strategies are optimization of regular analgesic medication combined with effective rescues medication. The new transmucosal forms of fentanyl represent an important improvement in our treatment options.

Cancer pain

Cancer pain management is in continuous innovation and new data are available that could change the therapeutical approach and guidelines. There are different fields of research that produce new data and interesting findings. The principal data regard the factors influencing the analgesic response, breakthrough cancer pain management, opioid switching, and pharmacogenetics. The findings reported in this review provide new ideas to be developed in further studies to confirm or not confirm some suggestive data.

Pharmacokinetics and Dose Proportionality of Fentanyl Sublingual Spray: a Single-Dose 5-Way Crossover Study

Fentanyl sublingual spray is a novel formulation of fentanyl for sublingual delivery that was designed to enhance the rate and extent of absorption of fentanyl for management of breakthrough cancer pain (BTCP). The primary objective of this study was to determine the pharmacokinetics and dose proportionality of 5 different doses (100, 200, 400, 600, and 800 μg) of fentanyl sublingual spray in healthy subjects under fasted conditions (part A); the secondary objective was to assess the effects of temperature and pH in the oral cavity on relative bioavailability of fentanyl (part B). Analyses were performed on venous blood samples drawn 5 min to 36 h after administration of fentanyl sublingual spray (Subsys(®), Insys Therapeutics, Inc., Chandler, AZ, USA). Part A of this phase I study was a 5-treatment, 5-sequence, 5-period crossover study in which subjects received a single treatment of each of the 5 fentanyl sublingual spray doses. Dose proportionality was assessed using analysis of variance and linear regression techniques. Part B was a 5-treatment, 2-sequence, 5-period crossover study in which subjects received a single assigned dose of fentanyl sublingual spray 200 μg under the following 5 conditions: no pretreatment, pretreatment with cold or hot beverage, and pretreatment with low- or high-pH beverage. Naltrexone was administered to block potential opioid effects associated with fentanyl. Adverse events (AEs) were monitored and recorded throughout the study. Fifty-three subjects (15 men, 38 women; mean age, 31 years) were enrolled in part A. Fourteen subjects (11 men, 3 women; mean age, 32 years) were enrolled in part B. The first quantifiable mean plasma concentrations of fentanyl were observed at the first sample time (5 min) for all doses. Mean maximum plasma concentration (C(max)) increased with increases in dose, whereas median time to reach C max (t max) tended to decrease with increases in dose. The dose-normalized C(max), area under the plasma concentration-time curve from time zero to infinity (AUC∞), and AUC from time zero to time of last measurable concentration (AUClast) values were linear and consistent with dose proportionality across the 100-800 μg dose range. Pretreatment of the oral cavity with a cold or hot beverage, or low- or high-pH beverage, did not appreciably alter fentanyl absorption (C(max) and AUC∞ values). The most commonly reported AEs were nausea and vomiting. In healthy subjects, administration of fentanyl sublingual spray produced a rapid rise in fentanyl plasma concentrations. Dose-dependent parameters (C max and AUC) showed dose proportionality across the range of 100-800 μg. Altering the local environment of the oral cavity (temperature and pH) showed no effects on the bioavailability of fentanyl. The rapid and predictable rise in plasma fentanyl concentrations following administration of fentanyl sublingual spray corresponds with the rapid onset and duration of many BTCP episodes.

The use of fentanyl buccal tablets for breakthrough pain by using doses proportional to opioid basal regimen in a home care setting

The dose of rapid onset opioids to be given for breakthrough cancer pain (BTcP) is controversial. Dose proportional to the basal opioid regimen seem to be safe and effective in hospital units. However, data in other less protected settings, like home care, are lacking. The aim of this open-label study was to assess the efficacy and safety in a group of patients with BTcP followed at home, after giving a dose of fentanyl buccal tablets (FBT) proportional to the opioid basal regimen, skipping the steps for dose titration. Consecutive patients admitted to a home care program presenting BTcP episodes and receiving stable doses of opioids for background pain were selected. Data from four consecutive episodes of BTcP were collected. For each episode, patients were instructed to routinely collect changes in pain intensity and severe adverse effects when pain got severe (T0) and to reassess the same items 15 min after FBT, given as a rescue medication in doses proportional to the daily opioid doses used for background pain (T15). One hundred twenty episodes of BTcP were recorded in 30 patients. One hundred eight episodes were defined as successfully treated, while 12 episodes required a further administration of opioids. Pain intensity significantly decreased at T15 (p < 0.001). In 95.5 and 90.8 % of episodes treated, there was a reduction in pain intensity of more than 33 and 50 %, respectively. No relevant adverse effects were recorded, even in older patients. This study suggests that FBT given in doses proportional to the basal opioid regimen for the management of BTcP is very effective and safe in clinical practice in the home care setting.

Fentanyl pectin nasal spray: a novel intranasal delivery method for the treatment of breakthrough cancer pain

Fentanyl pectin nasal spray is a novel intranasal formulation for the management of breakthrough cancer pain in patients taking and tolerant to opioids for persistent cancer pain. The pectin-based delivery modulates the product’s transmucosal absorption. Nasal delivery allows fentanyl pectin nasal spray to achieve a greater maximum plasma concentration than oral transmucosal fentanyl products and at a much faster rate. Compared with intranasal fentanyl compounded with aqueous solutions, the pectin-based system decreases the maximum plasma concentration and prolongs exposure to more closely match the time course of a typical breakthrough cancer pain episode. Throughout all phases of clinical studies, it was shown to be safe and effective in doses between 100 and 800 µg per breakthrough pain episode. Fentanyl pectin nasal spray is the only proprietary intranasal fentanyl formulation in the USA and one of two in Europe. Owing to the medication’s delivery system, the pharmacokinetics and subsequent dosing are unique to this product and should not be interchanged with any other proprietary or compounded fentanyl product.

How nurses assess breakthrough cancer pain, and the impact of this pain on patients' daily lives – Results of a European survey

PurposeTo increase our knowledge of how nurses assess breakthrough cancer pain (BTCP); and whether they find it difficult to distinguish BTCP from background pain; how they estimate the impact of BTCP on patients' daily lives, and the factors that nurses consider to induce BTCP. Variations in their use of assessment tools and their ability to distinguish between different types of pain were also examined in terms of the number of years of oncology nursing experience and the practice in different countries. MethodsIn total, 1241 nurses (90% female) who care for patients with cancer, from 12 European countries, completed a survey questionnaire. Key resultsHalf the sample had >9 years of experience in oncology nursing. Although 39% had no pain assessment tool to help them distinguish between types of pain, 95% of those who used a tool found it useful. Furthermore, 37% reported that they had problems distinguishing background pain from BTCP. Movement was identified as the factor that most commonly exacerbated BTCP across all countries. The nurses reported that BTCP greatly interfered with patients' everyday activities, and they rated the patients' enjoyment of life as most strongly affected. The use of tools and the ability to distinguish between different pains varied between European countries and with years of experience in oncology nursing. ConclusionsThe nurses reported that BTCP greatly interfered with patients' lives, and many nurses had problems distinguishing between background pain and BTCP. Nurses require more knowledge about BTCP management, and guidelines should be developed for clinical use.

Optimal management of breakthrough cancer pain (BCP)

Breakthrough cancer pain (BCP) is common in patients with cancer, causing a negative impairment in quality of life. Recent diagnostic criteria allow for differentiation of background chronic pain and BCP, for which proportion of unpredictable episodes is very high. Five characteristics define BCP: rapid onset, high intensity, maximum intensity (minutes), mean duration 30 min, and unpredictable onset. Fentanyl is a synthetic opioid characterized by rapid absorption and start of the analgesic effects. In addition to comparing some of the marked differences between the four pharmaceutical forms of fentanyl marketed in Spain, this paper discusses the data collected in a comprehensive clinical trial program with fentanyl pectin nasal spray (FPNS), a formulation that takes advantage of the intranasal route and the PecSys™ technology. The FPNS formulation achieves analgesic action 5 min after application and significant pain relief at 10 min. FPNS, therefore, has key features to be an optimal treatment for BCP.

Breakthrough cancer pain &amp;ndash; still a challenge

Breakthrough cancer pain is defined as transient pain exacerbation in patients with stable and controlled basal pain. Although variable, the prevalence of breakthrough cancer pain is high (33%–95%). According to the American Pain Foundation, breakthrough pain is observed in 50%–90% of all hospitalized cancer patients, in 89% of all patients admitted to homes for the elderly and terminal-patient care centers, and in 35% of all ambulatory care cancer patients. The management of breakthrough cancer pain should involve an interdisciplinary and multimodal approach. The introduction of new fentanyl formulations has represented a great advance and has notably improved treatment. Among these, the pectin-based intranasal formulation adjusts very well to the profile of breakthrough pain attacks, is effective, has a good toxicity profile, and allows for convenient dosing – affording rapid and effective analgesia with the added advantage of being easily administered by caregivers when patients are unable to collaborate.

An evaluation of the use of traditional opioids and immediate-release fentanyl in the management of breakthrough cancer pain in an integrated cancer network

IntroductionBreakthrough cancer pain (BTcP) is common and is associated with significant morbidity. Immediate release Fentanyl products are licensed for the management of BTcP; however, some practical concerns exist about their...

Dosing fentanyl buccal tablet for breakthrough cancer pain: dose titration versus proportional doses

Objectives:The aim of this study was to compare the efficacy and safety of doses of fentanyl buccal tablet (FBT) proportional to doses of opioids used for background analgesia versus dose titration starting with the minimal dose for the management of breakthrough cancer pain (BTcP).Methods:A total of 82 cancer patients with BTcP who were receiving strong opioids in doses of at least 60 mg of oral morphine equivalents and having acceptable background analgesia, were selected for a multicenter unblinded study. Forty-one patients were randomized to receive FBT in doses proportional to the daily opioid doses for four consecutive episodes of BTcP (group P). Forty-one patients underwent dose titration of FBT, with an initial dose of 100 µg, for four consecutive episodes (group T). Pain intensity and symptoms associated with opioid therapy were measured before administering any dose of FBT (T0) and 15 minutes after (T15).Results:In all, 80 patients were considered for analysis (39 and 41 patients in group P and T, respectively). Patients were receiving a mean of 126 ± 100 mg of oral morphine equivalents (range 60–480 mg) for background analgesia. A total of 293 episodes of BTcP (144 and 149 in group P and T, respectively) were treated and considered for analysis. No differences were found in the decrease of pain intensity between the two groups. However, in patients receiving doses of oral morphine equivalents of >120 mg/day, a significant number of patients obtained a decrease in pain intensity >50% in group P in comparison with group T (p = 0.040). Also, the need for rescue medication was significantly more frequently reported in group T for the first episode of BTcP (p < 0.0005). No differences in the level of adverse effects were observed between the two groups. No differences in patients’ satisfaction were reported.Conclusion:According to the data obtained in this study, there is no evidence for the use of dose titration in the management of BTcP in opioid-tolerant patients. Indeed, doses proportional to basal opioid regimen for background pain seem to be effective and safe in the majority of patients. Further studies should confirm this data in patients receiving higher doses of opioids, with other rapid-onset opioids, and in other settings.

Efficacy and safety of fentanyl sublingual spray for the treatment of breakthrough cancer pain: a randomized, double-blind, placebo-controlled study

Background and objectives:A number of transmucosal fentanyl formulations have been developed for the management of breakthrough cancer pain (BTCP). Sublingual delivery of fentanyl, formulated as fentanyl sublingual spray, offers the potential for more rapid and greater absorption of fentanyl and associated onset of analgesic effect compared with other formulations. The objective of this study was to assess the efficacy and safety of fentanyl sublingual spray for the treatment of BTCP.Research design and methods:This was a randomized, double-blind, placebo-controlled phase III trial conducted in opioid-tolerant patients with BTCP. An open-label titration period was followed by a double-blind treatment period during which patients received fentanyl sublingual spray (100–1600 mcg) or placebo.Clinical trial registration:Trial registration: ClinicalTrials.gov identifier: NCT00538850.Main outcome measures:The primary efficacy measure was summed pain intensity difference at 30 minutes (SPID30). Secondary efficacy measures included total pain relief at 30 minutes (TOTPAR30) and patient global evaluation of study medication at 30 minutes. Efficacy measures were also assessed at various time points from 5–60 minutes postdose. Adverse events were monitored throughout the study.Results:A total of 130 patients were treated during the titration period, of whom 98 (75.4%) entered the double-blind period. Relative to placebo, fentanyl sublingual spray significantly improved mean SPID scores from 5 minutes (p = 0.0219) through 60 minutes (p < 0.0001), including the primary endpoint at 30 minutes (p < 0.0001). Fentanyl sublingual spray produced significantly greater pain relief (expressed in terms of TOTPAR) from 5 through 60 minutes (p < 0.0001), and significantly greater global evaluation of treatment effectiveness (p < 0.0001), compared with placebo. During double-blind treatment, the most frequently reported adverse events were nausea (7.1%), hyperhidrosis (5.1%), and peripheral edema (5.1%). Serious adverse events occurred in seven patients (5.4%) during titration and six (6.1%) during double-blind treatment; none were considered related to treatment.Conclusions:These findings indicate that treatment with fentanyl sublingual spray results in effective relief of BTCP, with a rapid onset of action, and is well tolerated.

Conductas aberrantes asociadas al empleo de fentanilos rápidos en pacientes oncológicos terminales: a propósito de un caso

We report the case of a 45 year old male terminal patient, with a previous history of alcohol and tobacco addiction, who developed aberrant behaviours associated with the use of a rapid onset fentanyl (oral transmucosal fentanyl citrate) as a rescue dose for the management of breakthrough cancer pain. The aberrant behaviours detected included, among others: addiction to the opioid, chemical coping, misuse, and self-medication. Once the behaviours were detected, the patient responded adequately to a strategy of open and assertive confrontation of the problem, and the establishing of a therapeutic contract with clear-cut limits. In the discussion we review our knowledge of the aberrant behaviours related to rapid onset fentanyl prescription, and we suggest some easy points that might raise the suspicion of the diagnosis. We also review known risk factors for these behaviours, suggested opioids for pain management under these circumstances, and the way to build an opioid treatment agreement.

The management of breakthrough cancer pain (BTCP) and the use of immediate release fentanyl products

BackgroundBreakthrough pain is a common problem for people with cancer, and is associated with significant morbidity in these individuals. The association of palliative medicine (APM) has produced guidelines for the...

Fentanyl Pectin Nasal Spray for Breakthrough Cancer Pain

Optimal management of breakthrough cancer pain (BTCP) requires analgesics with a rapid onset of action, consistent efficacy, improved patient acceptability and tolerability and ease of use. Fentanyl pectin nasal spray (FPNS) incorporates a proprietary pectin-based gelling agent to enhance absorption and produce a faster onset of action and consistent plasma concentration. FPNS is indicated for the treatment of breakthrough pain in cancer patients who are tolerant to opioid therapy for their underlying persistent cancer pain. FPNS has been evaluated in clinical studies in patients with BTCP and shown to be effective, safe and well tolerated. In addition, FPNS has demonstrated high levels of patient satisfaction, convenience and ease of use. FPNS therefore represents an important addition to the treatment options for BTCP.

Patient-Controlled Intrathecal Analgesia for the Management of Breakthrough Cancer Pain: A Retrospective Review and Commentary

Intrathecal therapy (ITT) via an implanted pump has become an accepted practice for the treatment of refractory cancer pain by infusing opioids and adjuncts directly to the neuraxis. Until recently, only a programmed basal rate of infusion could be delivered, and therefore, breakthrough pain required ongoing use of oral or transmucosal opioids. Recently, an implanted pump manufacturer has introduced a handheld device to bolus additional medication for breakthrough pain. We hypothesize that patient-controlled intrathecal analgesia (PCIA) for the treatment of breakthrough cancer pain reduces the need for breakthrough opioids and improves the patient perception of pain. A retrospective chart review was done on all patients who underwent ITT for cancer pain between January 2009 and February 2011. Clinical outcomes of interest were reduction in nonintrathecal opioid use and reduction in numerical rating score (NRS) for pain. The data was collected prior to ITT and at a 4-6 week postimplant visit. After initiation of ITT with PCIA, 50% of patients had discontinued all nonintrathecal opioids at follow-up, and 46% of the patients on breakthrough medications no longer required their use. At follow-up, there was a significant reduction in total nonintrathecal opioid use, with an average of 796 mg pre-ITT vs 64 mg post-ITT of daily oral morphine equivalent dosing (P = <0.001). There was a significant difference between mean NRS pain score at follow-up-6.5 vs 3.1 pre-ITT (P<0.001). 65% of patients reported their pain as severe (NRS of 7 or greater) prior to ITT; this decreased to 3% at follow-up. In patients with refractory cancer pain, intrathecal drug therapy with PCIA is associated with improved pain reporting, reduced nonintrathecal around-the-clock, and breakthrough opioid requirements.

S612 UTILITY AND APPLICATION OF INSTANYL® POPULATION PHARMACOKINETIC METAANALYSIS FOR RATIONAL MANAGEMENT OF BREAKTHROUGH CANCER PAIN

European Journal of Pain SupplementsVolume 5, Issue S1 p. 272-273 S612 UTILITY AND APPLICATION OF INSTANYL® POPULATION PHARMACOKINETIC METAANALYSIS FOR RATIONAL MANAGEMENT OF BREAKTHROUGH CANCER PAIN N. Kaessner, N. Kaessner Nycomed, Konstanz, GermanySearch for more papers by this authorR. Nave, R. Nave Nycomed, Konstanz, GermanySearch for more papers by this authorS. Roepcke, S. Roepcke Nycomed, Konstanz, GermanySearch for more papers by this authorA. Facius, A. Facius Nycomed, Konstanz, GermanySearch for more papers by this authorG. Lahu, G. Lahu Nycomed, Konstanz, GermanySearch for more papers by this author N. Kaessner, N. Kaessner Nycomed, Konstanz, GermanySearch for more papers by this authorR. Nave, R. Nave Nycomed, Konstanz, GermanySearch for more papers by this authorS. Roepcke, S. Roepcke Nycomed, Konstanz, GermanySearch for more papers by this authorA. Facius, A. Facius Nycomed, Konstanz, GermanySearch for more papers by this authorG. Lahu, G. Lahu Nycomed, Konstanz, GermanySearch for more papers by this author First published: 30 January 2012 https://doi.org/10.1016/S1754-3207(11)70942-7Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume5, IssueS1September 2011Pages 272-273 RelatedInformation

The management of breakthrough cancer pain

Breakthrough cancer pain is a heterogeneous condition, and management should involve a thorough assessment, an individualized treatment plan, and a thorough re-assessment. This article will highlight the recommendations for the management of breakthrough cancer pain from a task group of the Science Committee of the Association for Palliative Medicine of Great Britain and Ireland, and briefly review the new opioid preparations that have been developed for breakthrough pain.