Steffen T Simon1, Marianne Kloke2, Bernd Alt-Epping3, Jan Gärtner4, Martin Hellmich5, Rebecca Hein5, Maren Piel6, Oliver A Cornely7, Friedemann Nauck3, Raymond Voltz6. 1. Department of Palliative Medicine and Clinical Trial Unit in Palliative Care, University Hospital of Cologne, Cologne, Germany; Center for Integrated Oncology (CIO) Cologne/Bonn, University Hospital of Cologne, Cologne, Germany. Electronic address: steffen@steffensimon.de. 2. Department of Palliative Medicine with Institute of Palliative Care, Kliniken Essen-Mitte, Essen, Germany. 3. Department of Palliative Medicine, University Medical Center Goettingen, Goettingen, Germany. 4. Clinic for Palliative Care, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 5. Institute of Medical Statistics, Informatics and Epidemiology (IMSIE), University of Cologne, Cologne, Germany. 6. Department of Palliative Medicine and Clinical Trial Unit in Palliative Care, University Hospital of Cologne, Cologne, Germany; Center for Integrated Oncology (CIO) Cologne/Bonn, University Hospital of Cologne, Cologne, Germany. 7. Clinical Trials Centre Cologne (CTCC), ZKS Köln, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Department I of Internal Medicine, University of Cologne, Cologne, Germany.
Abstract
CONTEXT: Episodic breathlessness is a frequent and burdensome symptom in cancer patients but pharmacological treatment is limited. OBJECTIVES: To determine time to onset, efficacy, feasibility, and safety of transmucosal fentanyl in comparison to immediate-release morphine for the relief of episodic breathlessness. METHODS: Phase II, investigator-initiated, multicenter, open-label, randomized, morphine-controlled, crossover trial with open-label titration of fentanyl buccal tablet (FBT) in inpatients with incurable cancer. The primary outcome was time to onset of meaningful breathlessness relief. Secondary outcomes were efficacy (breathlessness intensity difference at 10 and 30 minutes; sum of breathlessness intensity difference at 15 and 60 minutes), feasibility, and safety. Study was approved by local ethics committees. RESULTS:Twenty-five of 1341 patients were eligible, 10 patients agreed to participate (four female, mean age 58 ± 11, mean Karnofsky score 67 ± 11). Two patients died before final visits and two patients dropped-out because of disease progression leaving six patients for analysis with 61 episodes of breathlessness. Mean time to onset was for FBT 12.7 ± 10.0 and for immediate-release morphine 23.6 ± 15.1 minutes with a mean difference of -10.9 minutes (95% CI = -24.5 to 2.7, P = 0.094). Efficacy measures were predominately in favor for FBT. Both interventions were safe. Feasibility failed because of too much study demands for a very ill patient group. CONCLUSION: The description of a faster and greater relief of episodic breathlessness by transmucosal fentanyl versus morphine justifies further evaluation by a full-powered trial.
RCT Entities:
CONTEXT: Episodic breathlessness is a frequent and burdensome symptom in cancerpatients but pharmacological treatment is limited. OBJECTIVES: To determine time to onset, efficacy, feasibility, and safety of transmucosal fentanyl in comparison to immediate-release morphine for the relief of episodic breathlessness. METHODS: Phase II, investigator-initiated, multicenter, open-label, randomized, morphine-controlled, crossover trial with open-label titration of fentanyl buccal tablet (FBT) in inpatients with incurable cancer. The primary outcome was time to onset of meaningful breathlessness relief. Secondary outcomes were efficacy (breathlessness intensity difference at 10 and 30 minutes; sum of breathlessness intensity difference at 15 and 60 minutes), feasibility, and safety. Study was approved by local ethics committees. RESULTS: Twenty-five of 1341 patients were eligible, 10 patients agreed to participate (four female, mean age 58 ± 11, mean Karnofsky score 67 ± 11). Two patients died before final visits and two patients dropped-out because of disease progression leaving six patients for analysis with 61 episodes of breathlessness. Mean time to onset was for FBT 12.7 ± 10.0 and for immediate-release morphine 23.6 ± 15.1 minutes with a mean difference of -10.9 minutes (95% CI = -24.5 to 2.7, P = 0.094). Efficacy measures were predominately in favor for FBT. Both interventions were safe. Feasibility failed because of too much study demands for a very ill patient group. CONCLUSION: The description of a faster and greater relief of episodic breathlessness by transmucosal fentanyl versus morphine justifies further evaluation by a full-powered trial.
Authors: Miguel Angel Benítez-Rosario; Inmaculada Rosa-González; Enrique González-Dávila; Emilio Sanz Journal: Support Care Cancer Date: 2018-06-18 Impact factor: 3.603
Authors: Josephine L Feliciano; Julie M Waldfogel; Ritu Sharma; Allen Zhang; Arjun Gupta; Ramy Sedhom; Jeff Day; Eric B Bass; Sydney M Dy Journal: JAMA Netw Open Date: 2021-02-01