A Report on the Long-Term Use of Fentanyl Pectin Nasal Spray in Patients With Recurrent Breakthrough Pain

ContextAs patients with cancer are living longer, there is a need to ensure that treatments used for palliative care are well tolerated and effective during long-term use.ObjectivesTo investigate the long-term use of fentanyl pectin nasal spray (FPNS) for the treatment of breakthrough pain in cancer (BTPc) in patients receiving regular opioid therapy.MethodsAdult patients (N = 401) taking at least 60 mg/day oral morphine or equivalent, experiencing one to four episodes of BTPc a day, entered an open-label long-term study (NCT00458510). Patients had either completed an FPNS randomized controlled trial or were newly identified. Of these, 171 patients continued into an extension study. Up to four episodes of BTPc a day were treated with FPNS at 100–800 μg titrated doses. During the extension study, patients visited the clinic every four weeks for assessment and reporting of adverse events (AEs).ResultsThere were 163 patients with documented FPNS use. The mean duration of use was 325 days; 46 patients used FPNS for ≥360 days; the maximum duration was 44 months. Seventy percent of patients did not change their FPNS dose; 2% of patients withdrew from the study because of the lack of efficacy. The most common AEs, aside from disease progression, were insomnia, 9.9%; nausea, 9.4%; vomiting, 9.4%; and peripheral edema, 9.4%. The overall incidence of FPNS-related AEs was 11.1%, the most common being constipation (4.1%), with no apparent dose relationship. Ten patients (5.8%) experienced nasal AEs, most of which were mild or moderate.ConclusionFPNS appeared to provide sustained benefit and was well tolerated during long-term treatment of BTPc.     

Fentanyl buccal tablets for breakthrough pain in highly tolerant cancer patients: preliminary data on the proportionality between breakthrough pain dose and background dose

Context

Cancer patients receiving high doses of opioids as background medication are challenging, and it would be useful clinically to know whether a rapid-onset opioid (ROO) for breakthrough cancer pain (BTcP) may be started at a dose proportional to the background opioid dose.

Objectives

The aim of this study was to assess the efficacy and safety of the fentanyl buccal tablet (FBT) in doses proportional to the opioid dose administered for background analgesia in a sample of patients with BTcP who were receiving high doses of opioids.

Methods

Twelve patients who were receiving opioids for background analgesia at doses equivalent to more than 500 mg of oral morphine and had adequately controlled pain were prospectively recruited. BTcP was treated with proportional doses of FBT: patients receiving 600 mg of oral morphine equivalents were administered 1000 μg of FBT, patients receiving 900 mg of oral morphine equivalents were administered 1500 μg of FBT, and so on. For each episode of BTcP, trained nurses collected pain intensity (on a 0–10 numerical rating scale) and emerging problems when called for increases in pain considered to be severe in intensity by patients (T0) and 15 minutes after FBT administration (T15).

Results

Patients were receiving mean doses of oral morphine equivalents of 1340 mg (±585; range 720–2400). Seventy-nine events were treated with FBT (6.6 ± 4.9 for each patient). The median pain intensity of BTcP events was 8 (range 7–10), and the mean dose of FBT administered was 2233 μg (±975; range 1200–4000). In most events, a decrease in pain intensity >33% and >50% was observed (n = 14 and n = 48, respectively) 15 minutes after the administration of FBT. Data on 11 episodes were missed. Only six events were unsuccessfully treated. In all the patients, the level of adverse effects after FBT administration was mild and indistinguishable from that associated with the background opioid analgesia.

Conclusion

FBT in doses proportional to the high doses of opioids used for background analgesia was efficacious and well tolerated when administered for BTcP. Controlled studies with a specific design and a large number of patients should confirm such preliminary results.     

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.     

A Network Meta-Analysis of the Efficacy of Opioid Analgesics for the Management of Breakthrough Cancer Pain Episodes

ContextWith many medications available for the management of breakthrough cancer pain (BTCP), physicians may require additional guidance in selecting an appropriate medication to suit an individual patient's needs.ObjectivesTo identify all the evidence and assess the relative clinical value of currently approved BTCP medications.MethodsFollowing a systematic literature search (2007–2010), the results of 10 randomized controlled trials investigating the effects of BTCP medications (intranasal fentanyl spray [INFS], fentanyl pectin nasal spray, fentanyl sublingual tablets, fentanyl buccal soluble film, fentanyl buccal tablets, oral transmucosal fentanyl citrate, and morphine sulfate immediate release) were synthesized using a network meta-analysis. The main outcome was pain intensity difference (PID) relative to placebo up to 60 minutes after the intake of medication.ResultsINFS, fentanyl pectin nasal spray, fentanyl buccal tablet, and oral transmucosal fentanyl citrate showed greater PIDs relative to placebo than other BTCP medications 15 minutes after intake. All other medications showed greater PIDs relative to placebo at 30 minutes, except morphine sulfate immediate release, which did not show efficacy over placebo until 45 minutes. Only INFS produced clinically meaningful pain relief (absolute PID ≥2) at 15 minutes.ConclusionFrom current evidence, although all BTCP medications provided pain relief within the time frames assessed, transmucosal fentanyl medications achieved a greater level of pain relief in a shorter time frame than placebo or oral morphine.     

A multicenter, placebo-controlled, double-blind, multiple-crossover study of Fentanyl Pectin Nasal Spray (FPNS) in the treatment of breakthrough cancer pain

This randomized, double-blind, crossover study assessed the efficacy and tolerability of a new rapid onset nasal fentanyl formulation (Fentanyl Pectin Nasal Spray; FPNS) for breakthrough cancer pain (BTCP). Eighty-three of 114 patients experiencing one to four BTCP episodes/day while taking ?60 mg/day of oral morphine or equivalent successfully identified an effective dose of FPNS during a titration phase and entered a double-blind phase in which 10 BTCP episodes were treated with this effective dose (7) or placebo (3). Compared with placebo, FPNS significantly improved mean summed pain intensity difference (SPID) from 10 min (P < 0.05) until 60 min (P < 0.0001), including the primary endpoint at 30 min (P < 0.0001). FPNS significantly improved pain intensity (PI) scores as early as 5 min (P < 0.05); pain intensity difference (PID) from 10 min (P < 0.01); and pain relief (PR) scores from 10 min (P < 0.001). More patients showed a clinically meaningful (?2-point reduction in PI) pain reduction from 10 min onward (P ? 0.01) and 90.6% of the FPNS-treated versus 80.0% of placebo-treated BTCP episodes did not require rescue medication (P < 0.001). Approximately 70% of patients were satisfied or very satisfied with the convenience and ease of use of FPNS. Only 5.3% of patients withdrew from treatment due to adverse events, no significant nasal effects were reported, and 87% of patients elected to continue open-label treatment post-study. In this short-term study, FPNS was safe, well tolerated, and rapidly efficacious for BTCP.     

Consistency of efficacy, patient acceptability, and nasal tolerability of fentanyl pectin nasal spray compared with immediate-release morphine sulfate in breakthrough cancer pain

ContextWe recently reported that fentanyl pectin nasal spray (FPNS) provides superior pain relief from breakthrough cancer pain (BTCP) compared with immediate-release morphine sulfate (IRMS), with significant effects by five minutes and clinically meaningful pain relief from 10 minutes postdose.ObjectivesTo report the consistency of efficacy, tolerability, and patient acceptability of FPNS vs. IRMS.MethodsPatients (n = 110) experiencing one to four BTCP episodes/day while taking ≥60 mg/day oral morphine (or equivalent) for background pain entered a double-blind, double-dummy (DB/DD), multiple-crossover study. Those who completed an open-label titration phase (n = 84) continued to a DB/DD phase; 10 episodes were randomly treated with FPNS and overencapsulated placebo or IRMS and nasal spray placebo (five episodes each). Pain intensity (PI) and pain relief scores were assessed. Patient acceptability scores were assessed at 30 and 60 minutes. Safety and tolerability were assessed by adverse events (AEs) and nasal assessments.ResultsPer-episode analysis revealed that FPNS consistently provided relief from pain more rapidly than IRMS; by 10 minutes, there were significant differences in PI difference scores and in the percentages of episodes showing clinically meaningful pain relief (P < 0.05). Overall acceptability scores were significantly greater for FPNS than for IRMS at 30 (P < 0.01) and 60 (P < 0.05) minutes. Patients were “satisfied/very satisfied” with the convenience (79.8%) and ease of use (77.2%) of FPNS. Only 4.7% of patients withdrew from titration because of AEs; no significant nasal effects were reported.ConclusionThis study demonstrates that FPNS is efficacious, well accepted, and well tolerated by patients with BTCP.     

Long-term tolerability,efficacy and acceptability of fentanyl pectin nasal spray for breakthrough cancer pain

Purpose  

Previous studies show that fentanyl pectin nasal spray (FPNS) rapidly provides clinically meaningful pain relief in the treatment of breakthrough cancer pain (BTCP). This study assessed the long-term tolerability, acceptability and consistency of effect of FPNS in patients with BTCP.     

Intravenous morphine for breakthrough (episodic-) pain in an acute palliative care unit: a confirmatory study

The aim of this prospective cohort study was to confirm the safety of intravenous morphine (IV-M) used in doses proportional to the basal opioid regimen for the management of breakthrough pain and to record the nurse compliance on regularly recording data regarding breakthrough pain treated by IV-M. Over a one-year period, 99 patients received IV-M for breakthrough pain during 116 admissions. The IV-M dose was 1/5 of the oral daily dose, converted using an equianalgesic ratio of 1/3 (IV/oral). For each episode, nurses were instructed to routinely collect changes in pain intensity and emerging problems when pain became severe (T0), and to reassess the patient 15minutes after IV-M injection (T15). Nurses were unaware of the aim of the study and just followed department policy. In total, 945 breakthrough events treated by IV-M were recorded and the mean number of events per patient per admission was eight (95% confidence interval (CI) 6.9-9.5). The mean dose of IV-M was 12mg (95% CI 9-14mg). In the 469 events (49.6%) with a complete assessment, a decrease in pain of more than 33% and 50% was observed in 287 (61.2%) and 115 (24.5%) breakthrough events, respectively. The mean pain intensity decreased from 7.2 (T0) to 2.7 (T15). In eight episodes, no changes in pain intensity were observed and a further dose of IV-M was given. The remaining patients did not require further interventions. No clinical events requiring medical intervention were recorded. In this confirmatory study, IV-M was administered for the management of breakthrough pain in doses proportional to the basal opioid regimen to all patients, including older patients and those requiring relatively large doses. This did not result in life-threatening adverse effects in a large number of patients and was effective in most cases. The role of nurses is of paramount importance in monitoring and collecting data and gathering information for audit purposes on the unit.     

Pharmacokinetics of Fentanyl Buccal Tablet: A Pooled Analysis and Review

Fentanyl buccal tablet (FBT) is indicated for the treatment of breakthrough pain in patients who are already receiving and are tolerant to opioid therapy for underlying, persistent cancer pain. FBT is designed to enhance the rate and efficiency of absorption of fentanyl through the buccal mucosa. FBT was shown to be dose proportional from 100 to 1,300 μg. This analysis provides an overview of the pharmacokinetic profile of FBT based on pooled data from nine pharmacokinetic studies. In all, 365 healthy non‐opioid‐tolerant adults receiving naltrexone were included in the analysis. Single‐dose (100 to 1,300 μg) pharmacokinetic parameters were dose normalized to 100 μg. Pharmacokinetic measures included maximum observed plasma drug concentration (C_max), plasma drug concentration versus time curve from time zero to infinity (AUC_0–∞), time to reach C_max (T_max), apparent plasma terminal elimination rate constant, and elimination half‐life. After FBT administration, fentanyl was rapidly absorbed, with T_max ranging from 20 minutes to 4 hours postdose. Mean AUC_0–∞ was 1.49 ng?hour/mL, and mean C_max was 0.237 ng/mL. However, plasma fentanyl concentration reached 80% of C_max within 25 minutes and was maintained through 2 hours after administration. Based on the individual studies, bioequivalence was shown for sublingual and buccal tablet placement, and no significant effect of dwell time (duration of FBT presence in the oral cavity) was observed. The pharmacokinetic profile of FBT was characterized by rapid absorption, which is consistent with the rapid‐onset efficacy profile of FBT observed in clinical studies.     

Fentanyl Buccal Tablet for Breakthrough Cancer Pain: Why Titrate?

Breakthrough cancer pain is a significant problem for many patients with cancer because of the fast onset and often unpredictable nature of the pain episodes. The rapid onset opioids therefore have a central role to play in the management of breakthrough cancer pain. The rapid onset opioid fentanyl buccal tablet provides a fast analgesic effect and is easy to administer. However, titration of the medication is essential in order to optimize the management of pain. This is because individual patient characteristics, comorbidities, and other treatments may influence the absorption, pharmacokinetics, and pharmacodynamics of drugs. It is therefore important to individualize treatment by determining the effective dose for each patient, which is the dose that provides adequate analgesia and minimizes undesirable adverse effects. Data from clinical studies of fentanyl buccal tablet show that patients' effective doses ranged from 100 to 800 µg per episode, highlighting the need for the titration process. Following successful dose titration, treatment with fentanyl buccal tablet can achieve significant pain relief as early as 10 minutes after administration, resulting in a high level of patient satisfaction.     

Equipotent doses to switch from high doses of opioids to transdermal buprenorphine

Introduction  The aim of this study was to evaluate the equianalgesic ratio of transdermal buprenorphine (TD BUP) with oral morphine and TD fentanyl in a sample of consecutive cancer patients receiving stable doses of 120–240 mg of oral morphine or 50–100 μg of TD fentanyl, reporting adequate pain and symptom control. Materials, methods, and results  Patients receiving daily stable doses of opioids for more than 6 days, with no more than two doses of oral morphine (20 and 40 mg, respectively) as needed, were switched to TD BUP using a fentanyl–BUP ratio of 0.6:0.8 and an oral morphine–BUP ratio of 70:1. Opioid doses, pain and symptom intensity, global satisfaction, and number of breakthrough medication were recorded before switching (T0), 3 days after (T3), and 6 days after (T6). Eleven patients were recruited in a period of 1 year, and data were complete for ten patients. The mean age was 61.6 (SD 9.5), and five patients were males. No significant changes in pain and symptom intensity were found, except improvement in reported constipation (p = 0.014), as well as in global satisfaction with the analgesic treatment. No significant changes in breakthrough pain medication were observed. Conclusion  The results of this study suggest that stable patients receiving relatively high doses of oral morphine or TD fentanyl could be safely switched to TD BUP, by using a ratio of 70:1 and 0.6:0.8, respectively, maintaining the same level of analgesia.     

Efficacy and tolerability of intranasal fentanyl spray 50 to 200 μg for breakthrough pain in patients with cancer: A phase III,multinational, randomized,double-blind,placebo-controlled,crossover trial with a 10-month,open-label extension treatment period

Objective: This trial investigated the efficacy and long-term tolerability of intranasal fentanyl spray (INFS) 50 to 200 μg in the treatment of breakthrough pain in opioid-tolerant patients with cancer.Methods: This Phase III, double-blind, randomized, placebo-controlled, crossover trial was conducted at pain centers, anesthesiology departments, palliative care units, and oncology clinics in Austria, Denmark, France, Germany, and Poland. Eligible patients were adults with cancer receiving a stable dose of long-term opioid treatment for the control of background pain. Patients were treated at home with their effective dose of INFS (50, 100, or 200 μg) or inactive spray (placebo) in a randomized sequence for 3 weeks, followed by a 10-month, open-label tolerability phase during which they received their effective dose of INFS. Throughout the study, patients were allowed to use their usual rescue medication, which was recorded in patient diaries. The primary efficacy end point was the pain intensity difference at 10 minutes after study drug administration (PID₁₀), as assessed using an 11-point numeric rating scale (0 = no pain to 10 = worst pain imaginable). An effect size of 0.5 for PID was considered clinically relevant. The rate of response, defined as PID₁₀ >2, was also assessed. Adverse events (AEs) were recorded in patient diaries during the efficacy period and reported in monthly clinic visits and follow-up weekly telephone contacts during the extension period.Results: In all, 120 patients were enrolled and achieved an effective dose; 113 were randomized and 111 were included in the intent-to-treat analysis set (56 men, 55 women; mean [SD] age, 60.6 [9.45] years; mean weight, 70.3 kg [men] and 65.3 kg [women]; white race, 107 [96.4%]; INFS 50 μg, 18; INFS 100 μg, 48; INFS 200 μg, 45; placebo, 110). PID₁₀ with INFS was 2-fold that with placebo (adjusted means, 2.36 vs 1.10; adjusted difference, 1.26 [greater than the clinically relevant difference of 0.5]; P < 0.001). Additional analysis revealed that the mean response rate with all 3 doses of INFS was 51.1% versus 20.9% with placebo. The prevalence of AEs was 22/111 (19.8%) during the efficacy period, during which the most frequently reported AEs were nausea (5 [4.5%]) and vertigo (2 [1.8%]). No serious AEs were considered related to the study drugs. In all, 108 patients entered the extension period, with a mean duration of exposure to INFS of 134.9 days. Progression of underlying malignant disease was the most common AE reported during this period (55 [50.9%]); this event was not considered treatment related.Conclusions: In these opioid-tolerant patients with cancer, INFS at doses of 50, 100, and 200 μg was associated with an onset of activity at 10 minutes and effective treatment of breakthrough pain compared with placebo. All doses were generally well tolerated and clinically efficacious.     

Nebulized Fentanyl for Relief of Abdominal Pain

OBJECTIVE: To compare the efficacies of nebulized vs. intravenous fentanyl for the relief of abdominal pain. METHODS: This randomized, double-blind, double-placebo-controlled study compared nebulized and intravenous fentanyl (1.5 micro g/kg). Group I received intravenous fentanyl and nebulized saline. Group II received nebulized fentanyl and intravenous saline. Pain scores were measured at baseline and at 15 and 30 minutes after the study drug, using a 100-mm visual analog scale. Thirty minutes after the study drug, the subjects were offered rescue medication. The groups were compared for changes in pain scores at 30 minutes (primary outcome, t-test), changes in pain scores at 15 minutes (t-test), and need for rescue medication (Fisher's exact test). Significance was defined as p < 0.05. RESULTS: Fifty subjects (24 group I, 26 group II) were enrolled. The groups were similar with respect to mean baseline pain (72 mm group I, 74 mm group II) and demographics. A statistically significant difference in changes in pain scores at 15 minutes favoring group I (25 mm vs. 10 mm, p = 0.005) was not evident by 30 minutes (25 mm vs. 16 mm, p = 0.24). The groups were not different with respect to need for rescue medication (50% in group I compared with 69% in group II, p = 0.25). CONCLUSIONS: Nebulized fentanyl provides comparable analgesia to that of intravenous fentanyl.     

A Randomized,Double-Blind,Placebo-Controlled Study of Fentanyl Buccal Tablets for Breakthrough Pain: Efficacy and Safety in Japanese Cancer Patients

ContextRapid-onset opioids for treating breakthrough pain (BTP) in patients with cancer are needed in the Japanese care setting.ObjectivesTo examine the efficacy and safety of fentanyl buccal tablets (FBTs) for treating BTP in Japanese cancer patients.MethodsThis was a randomized, double-blinded, placebo-controlled study. In subjects receiving around-the-clock (ATC) opioids at doses of 30 mg or more to less than 60 mg or 60–1000 mg of oral morphine equivalents (low and high ATC groups), dose titration was started from 50 to 100 μg FBT, respectively. Subjects whose effective dose was identified were randomly allocated to a prearranged administration order of nine tablets (six FBTs and three placebos), one tablet each for nine episodes of BTP (double blinded). Efficacy and safety of FBT were assessed for patients overall, and also for the low and high ATC groups.ResultsA significant difference was observed between FBT and placebo for the primary endpoint of pain intensity difference at 30 minutes. The analgesic onset of FBT was observed from 15 minutes in several secondary variables (e.g., pain relief). Adverse events were somnolence and other events associated with opioids were mostly mild or moderate. Of the low and high ATC group subjects, an effective FBT dose was identified in 72.2% and 73.1%, respectively.ConclusionThe safety of FBT and its analgesic effect on BTP were confirmed in Japanese cancer patients receiving opioids. Our findings suggest that analgesic onset may occur from 15 minutes after FBT, and that FBT can be administered to patients with low doses of ATC opioids.     

Consistent and Clinically Relevant Effects with Fentanyl Buccal Tablet in the Treatment of Patients Receiving Maintenance Opioid Therapy and Experiencing Cancer‐Related Breakthrough Pain

Fentanyl buccal tablet (FBT) has shown efficacy and tolerability in patients with cancer‐related persistent pain treated with maintenance opioids. We conducted a combined analysis of two similarly designed, randomized, placebo‐controlled studies to further evaluate the consistency and clinical relevance of analgesia outcomes. Of the 252 patients enrolled, 150 fulfilled the criteria for efficacy analysis and experienced 1,417 breakthrough pain episodes. A consistently greater effect was noted with FBT vs. placebo on the following measures: improvements from baseline of ≥33% and ≥50% in pain intensity (PI), a ≥2‐point reduction in PI, and a score of ≥2 for pain relief. Improvements in these clinically meaningful efficacy measures were seen with FBT at 15 minutes (earliest common evaluation) and remained evident at 60 minutes (final common evaluation). They were also reflected in a more favorable global medication performance assessment for FBT over placebo. FBT was generally well tolerated; most adverse events were typical of potent opioid use in a cancer population. Application‐site (buccal) abnormalities were infrequent and led to withdrawal of three patients. There were no serious adverse events or deaths attributable to FBT. This analysis suggests that FBT provides an analgesic effect that is consistent across multiple clinically relevant efficacy measures.     

Fentanyl Tolerance in the Treatment of Cancer Pain: A Case of Successful Opioid Switching From Fentanyl to Oxycodone at a Reduced Equivalent Dose

Opioids are not generally deemed to have an analgesic ceiling effect on cancer pain. However, there have been occasional reports of tolerance to opioid development induced by multiple doses of fentanyl. The authors report a case of suspected tolerance to the analgesic effect of opioid, in which an increasing dose of fentanyl failed to relieve the patient's cancer pain symptoms, but opioid switching to oxycodone injections enabled a dose reduction to below the equivalent dose conversion ratio. The patient was a 60-year-old man diagnosed with pancreatic body carcinoma with multiple metastases. The base dose consisted of 12 mg/day of transdermal fentanyl patches (equivalent to 3.6 mg/day, 150 μg/h fentanyl injection), and rescue therapy consisted of 10 mg immediate-release oxycodone powders. Despite the total daily dose of fentanyl reaching 5.6 mg (equivalent to 560 mg oral morphine), the analgesic effect was inadequate; thus, an urgent adjustment was necessary. Due to the moderate dose of fentanyl, the switch to oxycodone injection was done incrementally at a daily dose equivalent to 25% of the fentanyl injection. The total dose of oxycodone was replaced approximately 53.5% of the dose of fentanyl prior to opioid switching.     

The Fentanyl Story

Fentanyl, introduced more than 50 years ago, has become the most often used opioid for intraoperative analgesia. Since the early 1990s the fentanyl patch has been available for management of chronic pain of all forms of cancer as well as the persistent, intense pain from many noncancerous maladies. More than a half dozen rapid-onset transmucosal fentanyl preparations have been developed, approved, launched, and popularized for “breakthrough” pain syndromes in the past 20 years. The purpose of this article is to describe why this opioid has become so important in the treatment of pain in modern clinical practice. The data indicate that fentanyl's popularity has occurred because it has minimal cardiovascular effects, does not result in increases in plasma histamine, is relatively short in onset of action and duration of effect, is easy and inexpensive to synthesize and prepare for the marketplace, and is now familiar to clinicians working in pain and perioperative medicine throughout the world.PerspectiveFentanyl has become one of the most important opioids in the management of pain because it is available for administration intravenously, transdermally, and transmucosally. Its flexibility, potency, familiarity, and physical characteristics explain why it has become so valuable to clinicians managing pain throughout the world.     

Effects of Prophylactic Subcutaneous Fentanyl on Exercise-Induced Breakthrough Dyspnea in Cancer Patients: A Preliminary Double-Blind,Randomized, Controlled Trial

ContextDyspnea is one of the most distressing symptoms in patients with cancer, and often worsens with breakthrough episodes on exertion. We hypothesized that fentanyl given prophylactically may alleviate breakthrough dyspnea.ObjectivesTo determine the feasibility of conducting a randomized trial of subcutaneous fentanyl in patients with cancer, and examine the effects of fentanyl on dyspnea, walk distance, vital signs, and adverse events.MethodsIn this double-blind, randomized, controlled trial, we asked ambulatory patients with breakthrough dyspnea to perform a baseline six minute walk test (6MWT), and then assigned them to either subcutaneous fentanyl or placebo 15 minutes before a second 6MWT. We documented the change in dyspnea Numeric Rating Scale (NRS) score, walk distance, vital signs, and adverse events between the first and second 6MWT.ResultsA total of 20 patients were enrolled (1:1 ratio) without attrition. Comparison between baseline and second walk showed that fentanyl was associated with significant improvements in dyspnea NRS score at the end of the 6MWT (mean [95% CI] −1.8 [−3.2, −0.4]), dyspnea NRS score at rest of 15 minutes after drug administration (−0.9 [−1.8, −0.04]), Borg Scale fatigue score at the end of the 6MWT (−1.3 [−2.4, −0.2]), 6MWT distance (+37.2 m [5.8, 68.6]), and respiratory rate (−2.4 [−4.5, −0.3]). Nonstatistically significant improvements also were observed in the placebo arm, with no difference between the two study arms. No significant adverse effects were observed.ConclusionProphylactic fentanyl was safe and improved dyspnea, fatigue, walk distance, and respiratory rate. We also observed a large placebo effect. Our results justify larger randomized controlled trials with higher fentanyl doses (clinicaltrials.gov registration: NCT01515566).     

Pregabalin Vs. Opioids for the Treatment of Neuropathic Cancer Pain: A Prospective,Head‐to‐Head,Randomized, Open‐Label Study

Objectives

Neuropathic cancer pain (NCP) is a common manifestation of cancer and/or its treatment. Treatment following the WHO analgesic ladder provides relief for the majority of cancer pain patients; however, concern remains that opioids may be less efficacious for neuropathic pain (NP) compared with nociceptive pain, often necessitating the use of higher doses. Adjuvants, such as pregabalin, have shown to be efficacious for the treatment of NP, although data come mostly from noncancer studies. The comparative efficacy and safety of opioids versus adjuvants has not been studied for NCP. The aim of this study was to directly compare pregabalin versus a strong opioid for the treatment of NCP.

Methods

A total of 120 patients, diagnosed with “definite” NCP, were randomized into two groups and received increasing doses of either oral pregabalin or transdermal fentanyl for 28 days. VAS score, patient satisfaction, need for opioid rescue, and adverse events (AEs) were recorded.

Results

In the pregabalin group, a significantly higher proportion of patients achieved at least 30% reduction in VAS compared with the fentanyl group (73.3%, 95% CI: 60.3%–83.93 vs. 36.7%, 95% CI: 24.5%–50.1%, P < 0.0001, respectively), while the percentage mean change from baseline was also significantly different [46% (95% CI: 39.5%–52.8%) for pregabalin and 22% (95% CI: 14.9%–29.5%) for fentanyl (P < 0.0001)]. Patient‐reported satisfaction was more frequent with pregabalin, while AEs and treatment discontinuations were more frequent in the fentanyl group.

Discussion

Prompt use of a neuropathic pain‐specific adjuvant, such as pregabalin, in NCP may lead to better control of the neuropathic component, with opioid‐sparing effects.