Breakthrough Cancer Pain Episodes Research Articles

Inhaled fentanyl aerosol through a drug-device combination for breakthrough cancer pain: A multicenter, randomized, double-blind, placebo-controlled trial.

e24058 Background: Breakthrough cancer pain (BTcP) can significantly impact the life quality of the cancer patient. Wide-used rapid-onset opioids (ROOs) for BTcP are transmucosal fentanyl-based preparations. Inhaled fentanyl demonstrated similar pharmacokinetic properties as intravenous administration in healthy volunteers. Fentanyl aerosol can be generated via hand-held drug-device delivery system, providing rapid, consistent multi-dose administration. Fentanyl inhalant was explored as alternative treatment of BTcP in cancer patients in this study to evaluate its efficacy, safety, and tolerability in BTcP patients with well-controlled background cancer pain. Methods: Adults ≥18 years with cancer are eligible if they were experiencing persistent cancer- or treatment-related pain with above mild severity and 1-4 episode occurrences daily. Each patient was treated and observed for 6 BTcP episodes (4 with fentanyl inhalant, 2 with placebo). During each episode, patients were allowed to inhale up to six shots within 1 hour. Pain intensity was recorded using 11-point Numerical Rating Scale (NRS) at predefined time points. The primary endpoint was the time-weighted Sum of Pain Intensity Difference scores at 30 minutes (SPID30) after the first inhalation. Results: 335 BTcP episodes in 59 patients were treated. SPID30 was analyzed using mixed model of repeated measures with treatment (fentanyl inhalant or placebo), BTcP episode, baseline pain intensity score as fixed factors, and subject as random factor. Mean SPID30 ± SD was -97.4 ± 48.43 for fentanyl-treated episodes, and -64.6 ± 40.25 for placebo-treated episodes. Based on treatment adjustment in the mixed covariance model, significant difference (p < 0.001) was reported with mean treatment difference of -27.7 (LS-mean ± SD, -94.2 ± 4.49 for fentanyl and -66.5 ± 4.86 for placebo). It enlarged at 60 minutes (SPID60) with a mean treatment difference of -57.9 (LS-mean ± SD, -231.4 ±105.14 for fentanyl and -162.2 ± 91.21 for placebo, p < 0.001). Significant differences in PID for episodes treated with fentanyl versus placebo were seen 4 minutes after the first dosing and maintained up to 60 minutes. Other endpoints showed statistical significance favoring fentanyl treatment, including the proportion of NRS ≤ 3, NRS pain scores decreased ≥ 33% or ≥ 50% from baseline after completion of BTcP treatment within 30 minutes of first dose, and Pain Relief Score Within 30 Minutes of the First Dose (PR30). Only 4.4% of BTcP episodes required rescue medication in fentanyl group. Major adverse events were mild or moderate in severity and were typical for opioid drugs. Conclusions: Fentanyl inhalant is safe, effective, and well-tolerated for managing BTcP. It provides a non-invasive route for systemic drug delivery and can be self-administered or given by family caregivers as personalized and regular pain management. Clinical trial information: NCT05531422 .

Retrospective Observational Study on the Characteristics of Pain and Associated Factors of Breakthrough Pain in Advanced Cancer Patients.

Objective This study aimed to conduct a retrospective observational study to understand the status of characteristics of pain and identify potential variables influencing the clinical presentation of breakthrough cancer pain (BTP) in advanced cancer patients. Methods Advanced cancer patients over 18 years of age; diagnosed with cancer of any type and stage III or IV in the palliative care ward with available data were enrolled between 2018 and 2020. Demographic data and pain-related information were collected by using structured electronic extraction form from Hospital Information System (HIS). Patients who had well-controlled background pain with an intensity ≤4 on a 0–10 numerical scale for >12 hours/day, the presence of transient exacerbations of pain with moderate-severe intensity (≧5), and clearly distinguish from background pain were regarded to have suffered BTP. Spearman correlation was conducted to explore the relationship between pain score and demographics characteristics. Factors significant in univariate analysis were included in the multiple regression model to explore independent predictive factors associated with the BTP. Results Of 798 advanced cancer patients, the mean age was 56.7 (SD = 11.84) years. Lung cancer (29.95%) was the most common cancer, and pain (93%) was the most common symptom. More than half (n = 428, 53.6%) of the patients experienced BTP. The median number of BTP episodes was 4 (IQR = 2, 7, range: 1–42). The median intensity of BTP was 6 (IQR = 6, 7, range 5–10). Patients with severe background pain or BTP had longer hospital stay and more symptoms. Besides, more severe background pain was related to higher activity of daily living. Intramuscular injection of hydromorphone hydrochloride was the main medication for BTP onset. Younger age, background pain, anorexia, and constipation were independently associated with the presentation of BTP. BTP pain intensity was independently associated with bloating. Symptom numbers were an independent factor and positively associated with BTP episodes. Conclusions BTP resulted in poor prognosis, which has a variable presentation depending on interdependent relationships among different characteristics. Good controlling of background pain and assessment of pain-related symptoms are essential for BTP management. BTP should be managed individually, especially the invisible pain among aged patients. Furthermore, BTP-related education and training were still needed.

Analyzing Differences in Perception between Oncologists and Patients to Adapt Pharmacological Treatment for Breakthrough Cancer Pain: Observational ADAPTATE Study.

Background: Transmucosal fentanyl (TF), used for breakthrough cancer pain (BTcP) treatment, has different formulations with distinctive attributes. The hypothesis is that, in shared decision making for the prevention of certain therapeutic problems, doctors and patients assign different value to the characteristics of treatment options. Aim: The aim of this study was to assess the discordance between the oncologists' opinion of attributes of TF and patients' expectations in BTcP treatment. Methods: This is a multicenter, cross-sectional observational study using simultaneous written surveys of doctors and patients suffering from BTcP episodes. The opinion of Spanish oncologists and patients regarding the importance of 14 different attributes of TF treatment (start of action, potency, duration, presentations and doses available, ease of use, titration, administration time, need for saliva, oral mucositis, rhinitis, adverse events, risk of abuse, evidence available, and need for instructions or health personnel to handle the medication), using two surveys, one for each group. Results: Sixty-three clinical oncologists and 272 patients participated in the study. The patients' satisfaction with and knowledge of BTcP treatment was 6.4 and 6.8 points, respectively (scale 1-9). The attributes with the highest relevance were shared by both groups, although their priority differed. Significant differences were observed in the greater importance given by oncologists (onset and duration of analgesia, need for saliva, presence of mucositis, and time required for patient education) and patients (risk of opioid abuse/aberrant behavior). Conclusion: Our results confirm that some aspects that most concern patients about the treatment of BTcP differ from those to which oncologists attach most importance. Increased patient awareness and education about BTcP and its treatment could lead to greater satisfaction and better patient involvement in therapeutic decisions. Certain barriers need to be overcome, such as lack of time in consultations and poor communication skills of oncologists that hinder patient health education.

Shared Decision-Making in Managing Breakthrough Cancer Pain in Patients With Advanced Cancer.

Background:Pain is a significant problem in patients with cancer. Breakthrough cancer pain contributes to the pain experience, but it is often underassessed and underrecognized. Shared decision-making (SDM), where patient preferences, goals, and concerns are discussed and integrated into a shared decision, can potentially foster earlier identification of pain, including breakthrough cancer pain, and improve pain management.Objectives:To explore the use of SDM to evaluate its impact on cancer pain management.Methods:This prospective, multisite study engaged patients with advanced cancer to explore the use of SDM in managing cancer pain using a digital platform with an expanded pain assessment. Decision preferences were noted and incorporated into care. Outcomes included pain and patient-perceived pain care quality.Results:51 patients with advanced cancer enrolled in the study. The mean pain score was 5 out of 10 throughout the three study time points. 88% of patients experienced breakthrough cancer pain of severe intensity at baseline and approximately 70% at visits two and three. The majority of breakthrough cancer pain episodes lasted longer than 30 minutes. The majority (86%) of participating patients desired shared decision-making or patient-driven decision-making. Most patients expressed satisfaction with the level of shared decision-making in managing their cancer pain. Breakthrough cancer pain remained significant for most patients.Conclusions:SDM incorporated into pain discussions has the potential to improve pain outcomes, but significant challenges remain in managing breakthrough cancer pain.

The Prevalence and Characteristics of Breakthrough Cancer Pain in Patients Receiving Low Doses of Opioids for Background Pain.

Simple SummaryThe aim of this study was to assess the prevalence and characteristics of breakthrough cancer pain (BTcP) in patients receiving low doses of opioids for background pain. This prospective study showed that in this population, BTcP prevalence was 69.8%. Many patients did not achieve a sufficient level of satisfaction with BTcP medications, particularly with oral morphine. Data also suggest that better optimization of background analgesia, though apparently acceptable, may limit the number of BTcP episodes.The aim of this study was to assess the prevalence and characteristics of breakthrough cancer pain (BTcP) in patients receiving low doses of opioids for background pain. A consecutive sample of advanced cancer patients receiving less than 60 mg/day of oral morphine equivalent (OME) was selected. Epidemiological data, background pain intensity, and current analgesic therapy were recorded. The presence of BTcP was diagnosed according to a standard algorithm. The number of BTcP episodes, intensity of BTcP, its predictability and triggers, onset duration, interference with daily activities, BTcP medications, satisfaction with BTcP medication, and time to meaningful pain relief were collected. A total of 126 patients were screened. The mean intensity of background pain was 2.71 (1.57), and the mean OME was 28.5 mg/day (SD15.8). BTP episodes were recorded in 88 patients (69.8%). The mean number/day of BTP episodes was 4.1 (SD 7.1, range 1–30). In a significant percentage of patients, BTcP was both predictable and unpredictable (23%). The BTcP onset was less than 20 min in the majority of patients. The mean duration of untreated episodes was 47.5 (SD 47.6) minutes. The mean time to meaningful pain relief after taking a BTcP medication was >20 min in 44.5% of patients. The efficacy of BTcP medication was not considered good in more than 63% of patients. Gender (females) (OR = 4.16) and lower Karnofsky (OR = 0.92) were independently associated with BTcP. A higher number of BTcP episodes/day was associated with gender (females) (p = 0.036), short duration of BTcP (p = 0.005), poorer efficacy of BTcP medication (none or mild) (p = 0.001), and late meaningful pain relief (p = 0.024). The poor efficacy of BTcP medication was independently associated with a higher number of episodes/day (OR = 0.22). In patients who were receiving low doses of opioids, BTcP prevalence was 69.8%. Many patients did not achieve a sufficient level of satisfaction with BTcP medications, particularly with oral morphine. Data also suggest that better optimization of background analgesia, though apparently acceptable, may limit the number of BTcP episodes.

Impact of individualized management of breakthrough cancer pain on quality of life in advanced cancer patients: CAVIDIOPAL study

PurposeThe main aim of the study was to assess the impact of individualized management of breakthrough cancer pain (BTcP) on quality of life (QoL) of patients with advanced cancer in clinical practice.MethodsA prospective, observational, multicenter study was conducted in patients with advanced cancer that were assisted by palliative care units. QoL was assessed with the EORTC QLQ-C30 questionnaire at baseline (V0) and after 28 days (V28) of individualized BTcP therapy. Data on background pain, BTcP, comorbidities, and frailty were also recorded.ResultsNinety-three patients completed the study. Intensity, duration, and number of BTcP episodes were reduced (p < 0.001) at V28 with individualized therapy. Transmucosal fentanyl was used in 93.8% of patients, mainly by sublingual route. Fentanyl titration was initiated at low doses (78.3% of patients received doses of 67 μg, 100 μg, or 133 μg) according to physician evaluation. At V28, mean perception of global health status had increased from 31.1 to 53.1 (p < 0.001). All scales of EORTC QLQ-C30 significantly improved (p < 0.001) except physical functioning, diarrhea, and financial difficulties. Pain scale improved from 73.6 ± 22.6 to 35.7 ± 22.3 (p < 0.001). Moreover, 85.9% of patients reported pain improvement. Probability of no ≥ 25% improvement in QoL was significantly higher in patients ≥ 65 years old (OR 1.39; 95% CI 1.001–1.079) and patients hospitalized at baseline (OR 4.126; 95% CI 1.227–13.873).ConclusionIndividualized BTcP therapy improved QoL of patients with advanced cancer. Transmucosal fentanyl at low doses was the most used drug.Trial registrationThis study was registered at ClinicalTrials.gov database (NCT02840500) on July 19, 2016.

Pain in cancer: The patient experience in Spain.

e19021 Background: For patients, pain management can be a therapeutic objective that is just as important as oncological treatment. The aim was to analyze the illness experience of a group of oncological patients with pain associated to cancer and episodes of breakthrough cancer pain (BTcP), as well as their opinions on the care received. Methods: This study is an initiative of the ECO Foundation (Oncology Excellence and Quality Foundation), undertaken with the methodological support of Francisco de Vitoria University. Descriptive, transversal, multicenter and ecological study. 47 oncologists participated. Each of them invited 6 patients that met the participation selection criteria (one patient every day for 6 consultation days). An anonymous patient questionnaire was used, produced by the Scientific Committee, so they could provide their personal opinions and scores on their oncological pain (categorical variables). The doctor was in charge of transcribing the aggregated data compiled by means of an online survey. Statistical package: version 21.0 IBM SPSS-Windows. Results: The 47 oncologists collected information from 275 patients whose average age was 62.4. 46.5% were women. Clinical profile of the patient: The most frequent location of the primary tumor was the lung (28%), followed by breast (15.3%) and the intestine/colon (13.1%). Almost half of the patients (46.2%) suffered from maximum intensity pain of 8 points or higher (on a scale of 0 to 10) within the last 24 hours. Despite this, 8 out of 10 patients reported that they are satisfied or very satisfied with their pain treatment. 43% of patients were worried about the possibility of addiction or side-effects as a result of the treatment. However, 95% expressed satisfaction with the information offered by their doctor regarding analgesic treatment. More than half of patients gave the impact of their pain on their general activity, mood, everyday work and enjoyment of life a score of ≥7 out of 10 (10 = completely impacted). Conclusions: Although the patient satisfaction level regarding the doctors’ pain management was high, there seems to be room for improvement in terms of pain control and the impact of pain on each patient’s life.

Breakthrough Pain in Patients with Lung Cancer. A Secondary Analysis of IOPS MS Study.

Aim: To characterize breakthrough cancer pain (BTcP) in patients with lung cancer. Methods: This was a secondary analysis of multicenter study of patients with BTcP. Background pain intensity and opioid dose were recorded. The number of BTcP episodes, their intensity, predictability, onset, duration and interference with daily activities were collected. Opioids used for BTcP, the mean time to meaningful pain relief after taking medication, satisfaction and adverse effects were assessed. Results: 1087 patients with lung cancer were examined. In comparison with other tumors, patients with lung cancer showed: higher background pain intensity (p = 0.006), lower opioid doses (p = 0.005), higher intensity of BTcP (p = 0.005), movement (79.5%) and cough (8.2%), as principal triggers for predictable BTcP (p < 0.009), larger BTcP interference with daily activity (p = 0.0001), higher use of adjuvants (p = 0.0001). No relevant differences in the other parameters examined were found. Conclusion: Patients with lung cancer have their own peculiarities, including higher basal and BTcP pain intensity and the use of more adjuvant drugs for background pain. The most frequent triggers for predictable BTcP are movement and cough. Future studies should be performed to analyze the prevalence of BTcP in patients with different lung cancers as well as the optimal management strategy for background pain and BTcP.

Patient Satisfaction with Fentanyl Pectin Nasal Spray in Breakthrough Cancer Pain Management During Radiotherapy for Head and Neck Cancer.

ObjectiveThe severity of breakthrough cancer pain (BTcP) impacts patients’ quality of life, increases the risk of anxiety and depression, lowers functional capacities, and may lead to poor compliance with cancer treatments. The aim of the current study was to assess, in a real-life setting, patient satisfaction with a fentanyl-pectin-nasal-spray (FPNS) for BTcP management in head and neck (H&N) cancer patients treated by radiotherapy.Materials and MethodsThis non-interventional, prospective study was conducted in 92 adult H&N-cancer patients undergoing radiotherapy and who started FPNS treatment for BTcP. Throughout the radiotherapy period, the patients completed self-diaries to assess their BTcP episodes, FPNS use, satisfaction on FPNS efficiency (primary outcome), tolerability and ease of use.ResultsPrior to FPNS treatment, 86% of the patients were experiencing ≤4 BTcP episodes/day. During the radiotherapy period, the BTcP episodes were treated with a median dose of 100µg of FPNS. Patients were “satisfied/very-satisfied” with the efficiency (73% of assessments), ease of use (87% of assessments) and tolerability (87% of assessments) of FPNS. In total, 27% of patients reported at least one adverse event related to FPNS and 4% of patients discontinued treatment due to adverse events. None of the adverse events were serious. Patient quality of life was maintained throughout the radiotherapy period.ConclusionThis study showed, in a real-life setting, that a clear majority of H&N cancer patients treated with FPNS for BTcP throughout radiotherapy expressed satisfaction with this analgesic treatment.

Breakthrough Cancer Pain in Patients Receiving Low Doses of Opioids for Background Pain.

This study aimed to assess the characteristics of breakthrough cancer pain (BTcP) in patients receiving low doses of opioids for background pain in comparison with patients receiving at least 60 mg of oral morphine equivalents (OME). Patients with advanced cancer receiving less than 60 mg/day of OME with episodes of BTcP were included in the analysis (group L). Data were compared with patients receiving doses of opioids ≥60 mg of OME (group H). Pain intensity, current analgesic therapy, number of BTcP episodes, intensity of BTcP, its predictability and triggers, onset duration, interference with daily activities, BTcP medications, and time to meaningful pain relief were collected. Adverse effects imputable to a BTcP medication were recorded. A total of 1,418 and 2,474 patients were included in groups L and H, respectively. A lower number of BTcP episodes (p = .005), a lower BTcP intensity (p = .0001), a faster BTcP onset (p = .024), and a longer time to meaningful pain relief after taking a BTcP medication (p = .009) were found in group L as compared with group H. In group L, BTcP interference on daily activity was less than in group H (p = .009). Patients in group L were less likely to be prescribed an opioid as BTcP medication in comparison with patients in group H (p = .0001). Opioid doses used for BTcP were significantly higher in group H. Patients in group L were more likely to be less satisfied (p = .003) than patients in group H. No adverse effects of severe intensity were reported in both groups. Patients receiving lower doses of opioids exhibit some differences in BTcP presentation: fewer episodes with lower intensity and a faster onset, a longer time to meaningful pain relief, and less satisfaction with BTcP medication. A relevant percentage of patients was receiving fentanyl preparations normally reserved for patients receiving higher doses of opioids. Breakthrough pain is present in patients receiving low doses of opioids. It has its own peculiarities: less frequent, lower intensity, faster onset, longer time to meaningful pain relief, and less satisfaction with medication. Many patients were prescribed fentanyl preparations, which are normally reserved for patients receiving higher doses of opioids.

Delphi Consensus on the Follow-up of Cancer Patients with Breakthrough Pain Under Opioid Treatment

Breakthrough cancer pain (BTcP) is one of the most common symptoms related to the disease and its treatment. Its management differs from that of chronic pain but there is not a wide consensus about fundamental aspects of BTcP definition, diagnosis, follow-up, and management. The objective of this study is to reach a consensus on the follow-up of patients with BTcP under opioid treatment. This work was conducted using a modified Delphi method organized in two rounds and involving a panel of 84 medical oncologists. A questionnaire of 66 items was developed with the following topics: (1) When to perform the first and subsequent BTcP treatment evaluations; (2) What to assess at the first follow-up visit and how; and (3) What to assess in the following visits and how. After two rounds, a consensus was reached in 53 of 66 items proposed (80.3%). The main agreements reached include: The first follow-up visit should preferably be face-to-face; increase the number of visits after detecting poor control of BTcP; assess pain control episodes of BTcP in the first and following visits; adjust treatment dose of opioids due to poor control of BTcP; and adopt measures to prevent aberrant opioid-induced behaviors when treating BTcP in patients with cancer. This Delphi consensus highlights the different points of view of medical oncologists regarding the follow-up of patients with BTcP under opioids treatment. Nonetheless, the conclusions reached can facilitate optimizing monitoring of these patients and promote long-term effectiveness of BTcP control.

Effects of Age Among Elderly Cancer Patients on Breakthrough Pain Management with Sublingual Fentanyl Tablets.

IntroductionSublingual fentanyl tablets (SFTs) have been shown to be a safe and effective option in controlling breakthrough cancer pain (BTcP). However, further examination is required to investigate the use of SFTs among the elderly. The aim of this study was to examine the influence of age in BTcP management with SFTs in the elderly population.MethodsWe performed subgroup analyses of a recently completed trial in two subsets of individuals: patients aged 65–74 years (low age group) and patients ≥ 75 years (high age group). Pain intensity (PI), onset of pain relief, frequency and duration of BTcP episodes, and adverse events (AEs) were assessed at 3, 7, 15, and 30 days. Health status instruments used were the Hospital Anxiety and Depression Scale (HADS-A and HADS-D) and the Short Form 12, version 2 (SF-12v2) questionnaire.ResultsLevels of PI at the end of the study improved significantly as compared with baseline in both the low and the high age groups (30.0% and 27.7% reduction, respectively). The onset of analgesia at the end of the study began in < 10 min in 85.0% of young–old subjects and in 62.5% of patients ≥ 75 years, but no significant differences were found. BTcP episodes lasted < 15 min in 75.0% of patients in the low age group and 58.3% in the high age group (p = 0.24). Most of patients in both groups experienced one to five BTcP daily episodes, at all assessment points. HADS-D decreased from 10.78 (± 4.33) to 8.21 (± 3.57) in the low age group, and from 10.96 (± 4.26) to 9.36 (± 3.35) in the high age group (p = 0.02). Significant differences in HADS-A scores from baseline to the end of the study were also observed in both subgroups (p < 0.05). Patients in the low age group had less favorable mental component summary (MCS) and physical component summary (PCS) scores than patients in the high age group. At the end of the study, 10.0% of young–old patients and 29.2% of patients aged ≥ 75 years reported AEs related to their treatment. The most commonly reported AEs included nausea, vomiting, constipation, somnolence, and skin disorders and they were generally mild to moderate in severity.ConclusionsThe results of this study showed that SFTs provided safe and clinically meaningful pain relief in both elderly subgroups. Clinical implications of these findings await validation in large, confirmatory studies to identify age subgroup divergences among elderly cancer patients treated with SFTs.

Effectiveness of fentanyl pectin nasal citrate in controlling episodes of breakthrough cancer pain triggered by routine radiotherapy procedures.

The aim of the study was to evaluate the effectiveness of fentanyl pectin nasal spray (FPNS) in controlling procedural breakthrough cancer pain (BTCP) in advanced cancer patients undergoing radiotherapy. This study involved 62 advanced cancer patients, with well-controlled background pain, who presented BTCP associated to routine radiotherapy procedures, treated with FPNS according to our protocol of administration. The BPE intensity was measured using a visual analog scale (VAS). The BTCP was triggered during the computed tomography simulation (79.3%) or treatment delivery (20.7%). Patients indicated a mean VAS of 8.8 (range 7-10) when attempting the procedure. After 4.5min (range 2-10) of the first FPNS dose, the majority of patients (85.5%) indicated a VAS of 4.3 (range 2-6). 15.5% of the patients did not respond after 15min; requiring a second dose. All these patients responded, reporting a mean VAS of 4.2 (range 4-6) after 3.0min (range 2-5) of the second dose. None of the patients required a third dose, nor reported an AE after the administration of FPNS. In our knowledge, our study is the one of highest recruitment, and with the fastest response of BTCP treated with FPNS reported in advanced cancer patients undergoing radiotherapy. FPNS has proven to be highly effective in reducing the intensity of procedural BTCP in a very short period of time.

Prevalence and characterization of breakthrough pain in cancer patients with proctalgia treated with 3D pelvic radiotherapy.

Radiotherapy-induced dysfunction of the gastrointestinal tract is common in cancer patients and has a significant impact on their quality of life. In this study, we investigated the prevalence of breakthrough cancer pain (BTcP) in patients undergoing 3D pelvic radiotherapy and who had proctalgia. This observational, multicenter, cross-sectional epidemiological study was performed in 13 Spanish hospitals. Data were obtained on the presence and characteristics of BTcP, demographics, common comorbidities, and treatments prescribed to the patients. The prevalence of BTcP in patients undergoing pelvic 3D external radiotherapy with proctalgia (N = 105) was 48.6% (95% CI 39.0-58.1%). BTcP was further characterized in 59 patients. The mean (± SD) intensity of the BTcP episodes was 7.45 ± 1.47 in a visual analog scale. We found several statistically significant associations between the descriptive variables of BTcP with demographic and clinical variables associated with the tumor or the patient, such as an increased number of BTcP episodes per day depending on the presence or absence of diabetes (p = 0.001, Chi-square) or time to the onset of pain relief depending on the location of the tumor (p = 0.019, Chi-square). Fentanyl was the drug of choice in BTcP episodes for 95% of the patients. This study demonstrated a high prevalence of BTcP prevalence in cancer patients undergoing pelvic 3D radiotherapy and with proctalgia. Although the variables determining the onset of BTcP are still unclear, our results could help in the design of future clinical studies addressing the treatment of BTcP in these patients.

Breakthrough Cancer Pain in Patients With Abdominal Visceral Cancer Pain

ObjectiveThe objective of this study was to assess the characteristics of breakthrough cancer pain (BTcP) in patients with abdominal cancer pain, and the eventual factors associated with its presentation. MethodsPatients with abdominal visceral cancer presenting BTcP were included in the analysis. Pain intensity, current analgesic therapy, number of BTcP episodes, intensity of BTcP, its predictability and triggers, onset (≤10 minutes or >10 minutes), duration, interference with daily activities, medications and doses currently used for BTcP, and time to meaningful pain relief were collected. Adverse effects imputable to a BTcP medication were recorded. ResultsFour hundred fourteen patients were included in the study. The mean background pain was 2.7 (SD 1.19) and most patients (97.6%) were receiving opioids. The mean number of BTcP episodes/day was 2.2 (SD 1.51). The mean intensity of BTcP was 7.3 (SD 1.32). BTcP onset was ≤10 minutes and >10 minutes in 271 (65.5%) and 143 patients (35.5%), respectively, and the mean duration was 52.6 minutes (SD 38.1). Interference of BTcP with daily activity was relevant for 340 patients (82%). In 122 patients (29.5%), BTcP was predictable and ingestion of food (n = 63, 51.6%) was the most frequent trigger. In comparison with unpredictable BTcP, postprandial BTcP had a lower intensity (P = 0.039), had a faster onset (P = 0.042), and was associated with the use of oxycodone/naloxone (P = 0.003), and less use of nonsteroidal anti-inflammatory drugs (P = 0.006). ConclusionPatients with abdominal visceral BTcP represent a subgroup with specific features of BTcP, particularly those with predictable BTcP. Ingestion of food was the prominent trigger for BTcP, having a faster onset and a lower intensity. This group of patients more frequently used oxycodone/naloxone or no anti-inflammatory drugs. These findings suggest consequential therapeutic decisions.

Active study: undetected prevalence and clinical inertia in the treatment of breakthrough cancer pain (BTcP)

To prove if there is clinical inertia in the identification and treatment of episodes of breakthrough cancer pain (BTcP), comparing actual results from clinical practice with clinical oncologists' prior perception. Observational and descriptive study, using information collected by practising medical oncologists, at three moments: (a) questionnaire regarding their professional judgement of the handling of patients with BTcP in their practice, (b) cross-sectional clinical screening, to detect possible existing cases of BTcP in a representative sample of their patients, (c) retrospective self-audit of clinical case histories of patients diagnosed with BTcP to find out about how it has been handled. A random sample on a state level of 108 specialists in medical oncology. 540 patients who suffer some type of cancer pain on the designated study date for each specialist (July-December 2016). The global prevalence of BTcP in the study sample covered 91.3% of the patients who were suffering some type of cancer pain. Barely 2% of the doctors surveyed suspected figures around this mark. 40.9% of the cases had not been previously detected as BTcP by their doctors. Although 90% of the patients who had previously been diagnosed with BTcP received a specific analgesic treatment for the symptoms, 42% of those patients with known BTcP were not able to control their episodes of pain. Clinical inertia is a serious problem in the handling of BTcP in medical oncology services, where it is the subject of a significantly low level of detection and treatment, despite the contrasting perception of specialists.

Fentanyl buccal tablets in the treatment of breakthrough cancer pain. German cohort of a pan-European multicentre study

Patients with breakthrough cancer pain (BtCP) experience significant limitations in their physical, mental and social functions. Fentanyl buccal tablets (FBT), a rapid onset opioid, are specifically indicated for the treatment of BtCP. The results of the German cohort of a pan-European study are presented. This included cancer pain patients from 32 German centers. Patients were on continuous opioid medication and had at least 4 BtCP episodes per day. After randomization to 2 groups, 66 patients started the titration of FBT with 100 μg (group A) and 200 μg (group B), respectively. All patients were titrated to their individual EAD, which could be a maximum of 800 μg FBT per episode, regardless of the initial dose. Subsequently, up to 8 BtCP episodes were treated with this EAD. At baseline and after treatment, patients assessed the effects of BtCP on their functional status using the modified BPI-7S and answered questions about the efficacy, simplicity, and ease-of-use of the treatment. Successful titration was achieved by 49 patients (74.2%). There was no statistically significant difference between group A and group B. The global score of the modified BPI-7S increased by 8.5 (± 12.8) points (from 34.7 ± 13.6 at the beginning to 26.2 ± 15.8 at the end of treatment), from which a statistically significant improvement in the quality of life of patients can be derived. Global patient contentment improved, most notably the rapid onset of 2.4 points to 3.4 points at the end of the study. 76.9% of patients found taking FBT simple or very simple.

Factors Influencing the Clinical Presentation of Breakthrough Pain in Cancer Patients.

Background: The aim of this study was to identify potential variables influencing the clinical presentation of breakthrough cancer pain (BTP). Methods: Cancer patients with a diagnosis of BTP were enrolled. Demographic and clinical characteristics, as well as background pain and BTP characteristics were collected. Multivariate analyses were conducted to assess the correlation between BTP characteristics and the variables examined. Results: Data of 4016 patients were analysed. Average daily number of BTP episodes was 2.4, mean intensity was 7.5, and a mean duration was 43.3 min. A short onset BTP was observed in 68.9% of patients. In 30.5% of patients BTP was predictable. There were 86.0% of participants who reported a marked interference of BTP with their daily activities. Furthermore, 86.8% of patients were receiving opioids for the management of BTP. The average time to meaningful pain relief was 16.5 min and 70.9% of patients were satisfied with their BTP medications. Age, head and neck cancer, Karnofsky, background pain intensity, predictable and fast onset BTP were independently associated with the number of BTP episodes. BTP pain intensity was independently associated with background pain intensity, fast onset BTP, and Karnofsky. Neuropathic pain mechanism was independently associated with unpredictable BTP. Variables independently associated with a longer duration of BTP were age, place of visit, cancer diagnosis, disease-oriented therapy, background pain intensity and mechanism, and unpredictable BTP. Age, Karnofsky, background pain intensity, fast onset, and long duration of BTP were independently associated with interference with daily activity. Conclusions: BTP has a variable presentation depending on interdependent relationships among its different characteristics.

Breakthrough cancer pain: The importance of the right treatment at the right time.

Confusion remains over the definition of breakthrough cancer pain (BTcP) potentially leading to delayed diagnosis and treatment. An on-line survey was conducted in four EU countries among relevant healthcare professionals and cancer patients diagnosed with BTcP. The roles of healthcare professionals (HCPs) were examined and their knowledge and use of available medications recorded. Patients were questioned on how BTcP affected their lives and on the medications they had received/were receiving. There was a 'time lag' of 58 and 13weeks in Germany and Spain respectively between the initial diagnosis of BTcP and its treatment. Four in ten oncologists across the four countries considered themselves not fully confident in their choice of the appropriate therapy. A quarter of patients in Germany, Italy and Spain and four in ten in France were treated only with increased dosages of the therapy already prescribed for their background pain - often morphine. Almost another quarter received morphine in addition to their treatment for background pain. Oncologists indicated a need for faster-acting treatments revealing a potential lack of awareness of rapid onset oral opioids and patients expressed a desire for more effective pain relief and better psychological support. There is a need for a universal definition of BTcP to facilitate earlier and more accurate diagnosis. It is essential that BTcP is treated immediately on diagnosis with therapies that more closely mirror its temporal characteristics to ensure that patients' desire for more effective pain relief is fulfilled. Many cancer patients suffered episodes of BTcP needlessly over many months due to missed diagnosis. Even after diagnosis, many physicians were not fully confident in their choice of 'rescue' therapy which perhaps is not surprising given the very low level of awareness of treatment guidelines, both national and international.

Non pharmacological interventions and non-fentanyl pharmacological treatments for breakthrough cancer pain: A systematic and critical review.

Oral opioids or other pharmacological or non-pharmacological interventions are often suggested in the management of breakthrough cancer pain (BTcP). The aim of this systematic and critical review was to analyse and critically comment the evidence of any non-fentanyl therapies proposed for BTcP. A systematic literature search was carried out to find studies providing clinical data on any treatment excluding fentanyl products. No data exist about the use of oral opioids. Some information is available on parenteral morphine in a large sample of patients and episodes of BTcP. For other treatments, including methadone, nitrous oxide, anti-inflammatory drugs, samarium, and gabapentin the existing data, observational and obtained in a small number of patients do not provide useful information to be generalized. Only ketamine, a drug difficult to use for many physicians, particularly in determined setting, provided some evidence according a randomized controlled double-blind study. Recommendations suggesting the use of oral opioids or other pharmacological and non-pharmacologic interventions for BTcP, are not based on any, even minimal evidence. These treatments are worthwhile of further investigation, particularly in determined conditions that should fit the pharmacokinetics of oral opioids.