Low-dose sublingual fentanyl improves quality of life in patients with breakthrough cancer pain in palliative care.

Aim: This subanalysis of the CAVIDIOPAL study evaluated the impact of individualized management of breakthrough cancer pain (BTcP) with fentanyl on the quality of life (QoL) of advanced cancer patients in Spanish palliative care units. Patients & methods: This was a prospective, observational, multicenter study. The European Organization for Research and Treatment of Cancer's QLQ-C30 questionnaire was used at baseline (V0) and visit 28 (V28). Results: Ninety-five patients were mainly treated with 67-133 µg fentanyl, showing a notable reduction in intensity (visual analog scale: 8.0 [V0] to 4.6 [V28]), frequency and duration of BTcP episodes shortly after the first 1-2 weeks of treatment, with significantly improved QoL (global health status: 31.1 [V0] to 53.1 [V28]). Conclusion: Low-dose sublingual fentanyl effectively reduced BTcP in advanced cancer patients in palliative care units, significantly improving QoL. Clinical trial registration: NCT02840500 (ClinicalTrials.gov).

After the CAVIDIOPAL study, we carried out an additional analysis to evaluate the impact of individualized management of breakthrough cancer pain, using the analgesic drug fentanyl, on quality of life (QoL) of advanced cancer patients receiving palliative care in Spain. We performed a prospective, observational, multicenter study, in which patients' QoL was assessed using a validated questionnaire at baseline (day 0) and after 28 days of fentanyl treatment. Of the 95 patients included in the study, the majority were treated with low doses of fentanyl and showed significant pain relief. The intensity, frequency and duration of breakthrough cancer pain episodes were notably reduced shortly after the first 1­2 weeks of treatment. Moreover, patients' QoL significantly improved during fentanyl treatment from baseline to day 28. A global impression of improvement was reported by both patients and clinicians.

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

PURPOSE: The 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. METHODS: A 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. RESULTS: Ninety-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). CONCLUSION: Individualized BTcP therapy improved QoL of patients with advanced cancer. Transmucosal fentanyl at low doses was the most used drug. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov database (NCT02840500) on July 19, 2016.

Switching Ratio from Parenteral to Oral Methadone 1:1.2 Is Safer Compared with Ratio 1:2 in Patients with Controlled Cancer Pain: A Multicenter Randomized-Controlled Trial (RATIOMTD-010810).

Background: The most commonly used switching ratio from parenteral to oral methadone is 1:2. Methadone is highly bioavailable and a lower ratio might result in similar analgesia with less toxicity. Objective: To compare success and side effects with two ratios from parenteral to oral methadone: 1:2 versus 1:1.2 in hospitalized patients with cancer pain. Design: A multicenter double-blind randomized clinical trial. Settings/Particiants: Inpatients with well-controlled cancer pain with parenteral methadone requiring rotation to the oral route. Measurements: Outcomes included pain intensity (Brief Inventory Pain), opioid toxicity (Common Toxicology Criteria for Adverse Events), and methadone dose. Success was defined as no toxicity with good pain control at 72 hours. Results: Thirty-nine of forty-four randomized patients were evaluable: 21 in ratio 1:2 and 18 in ratio 1:1.2. Seventy-one percent male. Median age 65 years. No significant differences in basal clinical characteristics between both groups. Median methadone dose pre/post switching was 24.5 mg ±13.5 and 49 mg ±27.3 for ratio 1:2, versus 23.3 mg ±9.4 (p: not significant) and 28 mg ±11.3 (p < 0.01) for ratio 1:1.2. Pain was well controlled without differences between both ratios. Drowsiness at day +1 (p < 0.017) and myoclonus at day +3 (p < 0.019) were more prevalent in group 1:2. Success was observed in 12 patients in ratio 1:2 versus 18 in ratio 1:1.2 (p < 0.001). Methadone side effects were observed in 12 patients in ratio 1:2 (mainly neurotoxicity symptoms) versus 2 in ratio 1:1.2 (p < 0.005). Conclusion: Ratio 1:1.2 when changing from parenteral to oral methadone resulted in lower toxicity and no difference in analgesia. More conservative dose adjustment during methadone route change should be considered. European Clinical Trials Register (EudraCT No. 2010-024092-39).

Prevalence and characteristics of breakthrough cancer pain in an outpatient clinic in a Catalan teaching hospital: incorporation of the Edmonton Classification System for Cancer pain into the diagnostic algorithm.

BACKGROUND: Breakthrough cancer pain (BTcP) is defined according to its principal characteristics: high intensity, short time interval between onset and peak intensity, short duration, potential recurrence over 24 h and non-responsiveness to standard analgesic regimes. The Edmonton Classification System for Cancer Pain (ECS-CP) is a classification tool that evaluates different dimensions of pain. The aim of this study was to measure prevalence and the main characteristics of BTcP in a sample of advanced cancer patients and to explore the complexity observed when ECS-CP is incorporated into BTcP diagnostics algorithm. METHODS: Descriptive prevalence study (Retrospective chart review). Davies' algorithm was used to identify BTcP and ECS-CP was used to recognize appropriate dimensions of pain. The study was conducted in a sample of advanced cancer patients attending hospital outpatient clinic in Lleida, Spain. 277 patients were included from 01/01/2014 to 31/12/2015. No direct contact was made with participants. The following information was extracted from the palliative care outpatient clinic database: age, gender, civil status, cognitive impairment status, functional performance status and variables related to tumour. Only BTcP cases were included. RESULTS: Prevalence of BTcP was 39.34% (63.9% men). Mean of age was 68.2 years. Main diagnosis was lung cancer (n = 154; 31.6%). Metastases were diagnosed in 83% of the sample. 138 patients (49.8%) were diagnosed with 1 type of BTcP and 139 (50.2%) were diagnosed with more than one type of BTcP. In total, 488 different types of BTcP were recorded (mean 1.75 ± 0, 9), 244 of these types (50%) presented a component of neuropathic pain. Addictive behaviour, measured through CAGE test, was present in 29.2% (N = 81) of the patients and psychological distress was present in 40.8% (n = 113). CONCLUSIONS: Prevalence of BTcP (39.34%) is similar to the one reflected in the existing literature. Study results indicate that the routine use of ECS-CP in a clinical setting allows us to detect more than one type of BTcP as well as additional complexity associated with pain (neuropathic, addictive behavior and psychological distress).