Journal article
Randomized Phase 2 Trial of a Novel Clonidine Mucoadhesive Buccal Tablet for the Amelioration of Oral Mucositis in Patients Treated With Concomitant Chemoradiation Therapy for Head and Neck Cancer.
- Giralt J Hospital Vall d'Hebron, Barcelona, Spain; Vall d'Hebron Institute of Oncology, Barcelona, Spain.
- Tao Y Institut Gustave Roussy, Villejuif, France.
- Kortmann RD Department of Radiation Oncology, University of Leipzig, Germany.
- Zasadny X Clinique François Chénieux, Service de Radiothérapie, Limoges, France.
- Contreras-Martinez J Hospital Carlos Haya Oncología Radioterápica, Malaga, Spain.
- Ceruse P Centre Hospitalier Lyon Nord, Lyon, France.
- Arias de la Vega F Hospital de Navarra, Pamplona, Spain.
- Lalla RV University of Connecticut Health Center, Farmington, Connecticut.
- Ozsahin EM Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
- Pajkos G Bács-Kiskun Megyei Kórház Szegedi Tudományegyetem Általános Orvostudományi Kar Oktató Kórháza Onkoradiológiai Központ, Kecskemét, Hungary.
- Mazar A Monopar Therapeutics, Wilmette, Illinois.
- Attali P Onxeo, Paris, France.
- Bossi P Medical Oncology, University of Brescia, ASST-Spedali Civili, Brescia, Italy.
- Vasseur B Onxeo, Paris, France.
- Sonis S Primary Endpoint Solutions, LLC, Brigham and Women's Hospital and the Dana-Farber Cancer Institute, Boston, Massachusetts.
- Henke M Section Clinical Studies, Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany. Electronic address: henke@uni-freiburg.de.
- Bensadoun RJ Centre de Haute Energie, Nice, France.
- 2019-11-01
Published in:
- International journal of radiation oncology, biology, physics. - 2020
Administration, Buccal
Adult
Aged
Analgesics, Opioid
Chemoradiotherapy
Clonidine
Confidence Intervals
Deglutition Disorders
Double-Blind Method
Drug Administration Schedule
Female
Head and Neck Neoplasms
Humans
Male
Middle Aged
Placebos
Radiation-Protective Agents
Radiotherapy Dosage
Squamous Cell Carcinoma of Head and Neck
Stomatitis
Tablets
Young Adult
English
PURPOSE
Oral mucositis (OM) is a frequent and painful sequela of concomitant chemoradiation (CRT) used for the treatment of head and neck cancer (HNC) for which there is no effective intervention. This randomized, placebo-controlled study evaluated the efficacy of a novel, mucoadhesive topical tablet formulation of clonidine in mitigating CRT-induced OM in patients with HNC.
METHODS AND MATERIALS
Patients with HNC undergoing adjuvant radiation therapy (60-66 Gy; 5 × 1.8-2.2 Gy/wk) with concomitant platinum-based chemotherapy received daily local clonidine at 50 μg (n = 56), 100 μg (n = 65), or placebo (n = 62) via a topical mucobuccal tablet starting 1 to 3 days before and continuing during treatment. The primary endpoint was the incidence of severe OM (severe OM [SOM], World Health Organization grade 3/4).
RESULTS
SOM developed in 45% versus 60% (P = .06) of patients treated with clonidine compared with placebo and occurred for the first time at 60 Gy as opposed to 48 Gy (median; hazard ratio, 0.75 [95% confidence interval, 0.484-1.175], P = .21); median time to onset was 45 versus 36 days. Opioid analgesic use, mean patient-reported mouth and throat soreness, and CRT compliance were not significantly different between treatment arms. Adverse events were reported in 90.8% versus 98.4%, nausea in 49.6% versus 71.0%, dysphagia in 32.8% versus 48.4%, and reversible hypotension in 6.7% versus 1.6% of patients on clonidine versus placebo, respectively.
CONCLUSIONS
Although the primary endpoint was not met, the positive trends of OM-associated outcomes suggest that the novel mucoadhesive tablet delivery of clonidine might favorably affect the course and severity of CRT-induced SOM and support further evaluation.
Oral mucositis (OM) is a frequent and painful sequela of concomitant chemoradiation (CRT) used for the treatment of head and neck cancer (HNC) for which there is no effective intervention. This randomized, placebo-controlled study evaluated the efficacy of a novel, mucoadhesive topical tablet formulation of clonidine in mitigating CRT-induced OM in patients with HNC.
METHODS AND MATERIALS
Patients with HNC undergoing adjuvant radiation therapy (60-66 Gy; 5 × 1.8-2.2 Gy/wk) with concomitant platinum-based chemotherapy received daily local clonidine at 50 μg (n = 56), 100 μg (n = 65), or placebo (n = 62) via a topical mucobuccal tablet starting 1 to 3 days before and continuing during treatment. The primary endpoint was the incidence of severe OM (severe OM [SOM], World Health Organization grade 3/4).
RESULTS
SOM developed in 45% versus 60% (P = .06) of patients treated with clonidine compared with placebo and occurred for the first time at 60 Gy as opposed to 48 Gy (median; hazard ratio, 0.75 [95% confidence interval, 0.484-1.175], P = .21); median time to onset was 45 versus 36 days. Opioid analgesic use, mean patient-reported mouth and throat soreness, and CRT compliance were not significantly different between treatment arms. Adverse events were reported in 90.8% versus 98.4%, nausea in 49.6% versus 71.0%, dysphagia in 32.8% versus 48.4%, and reversible hypotension in 6.7% versus 1.6% of patients on clonidine versus placebo, respectively.
CONCLUSIONS
Although the primary endpoint was not met, the positive trends of OM-associated outcomes suggest that the novel mucoadhesive tablet delivery of clonidine might favorably affect the course and severity of CRT-induced SOM and support further evaluation.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1016/j.ijrobp.2019.10.023
- PMID 31669562
- Persistent URL
- https://sonar.ch/global/documents/139161
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