EffenDys-Fentanyl Buccal Tablet for the Relief of Episodic Breathlessness in Patients With Advanced Cancer: A Multicenter, Open-Label, Randomized, Morphine-Controlled, Crossover, Phase II Trial.
Episodic breathlessness is a frequent and burdensome symptom in cancer patients but pharmacological treatment is limited.



To determine time to onset, efficacy, feasibility, and safety of transmucosal fentanyl in comparison to immediate-release morphine for the relief of episodic breathlessness.



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.



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.



The description of a faster and greater relief of episodic breathlessness by transmucosal fentanyl versus morphine justifies further evaluation by a full-powered trial.
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.
Steffen T
ST
Simon
Department of Palliative Medicine with Institute of Palliative Care, Kliniken Essen-Mitte, Essen, Germany.
Marianne
M
Kloke
Department of Palliative Medicine, University Medical Center Goettingen, Goettingen, Germany.
Bernd
B
Alt-Epping
Clinic for Palliative Care, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Jan
J
Gärtner
Institute of Medical Statistics, Informatics and Epidemiology (IMSIE), University of Cologne, Cologne, Germany.
Martin
M
Hellmich
Institute of Medical Statistics, Informatics and Epidemiology (IMSIE), University of Cologne, Cologne, Germany.
Rebecca
R
Hein
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.
Maren
M
Piel
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.
Oliver A
OA
Cornely
Department of Palliative Medicine, University Medical Center Goettingen, Goettingen, Germany.
Friedemann
F
Nauck
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.
Raymond
R
Voltz
D000278:Administration, Buccal; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects; D018592:Cross-Over Studies; D018450:Disease Progression; D004417:Dyspnea / Q000188:drug therapy* / Q000209:etiology; D005240:Feasibility Studies; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage; D009369:Neoplasms / Q000150:complications*; D010352:Patient Dropouts; D010865:Pilot Projects; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
D000701:Analgesics, Opioid; D009020:Morphine; D005283:Fentanyl
Episodic breathlessness; cancer; fentanyl; morphine