Doxepin rinse versus placebo in the treatment of acute oral mucositis pain in patients receiving head and neck radiotherapy with or without chemotherapy: A phase III, randomized, double-blind trial (NCCTG-N09C6 [Alliance])

James L. Leenstra, Robert C. Miller, Rui Qin, James A. Martenson, Kenneth J. Dornfeld, James D. Bearden, Dev R. Puri, Philip J. Stella, Miroslaw A. Mazurczak, Marie D. Klish, Paul J. Novotny, Robert L. Foote, Charles Lawrence Loprinzi

Research output: Contribution to journalArticle

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Abstract

Purpose: Painful oral mucositis (OM) is a significant toxicity during radiotherapy for head and neck cancers. The aim of this randomized, double-blind, placebo-controlled trial was to test the efficacy of doxepin hydrochloride in the reduction of radiotherapy-induced OM pain. Patients and Methods: In all, 155 patients were randomly allocated to a doxepin oral rinse or a placebo for the treatment of radiotherapy-related OM pain. Patients received a single dose of doxepin or placebo on day 1 and then crossed over to receive the opposite agent on a subsequent day. Pain questionnaires were administered at baseline and at 5, 15, 30, 60, 120, and 240 minutes. Patients were then given the option to continue doxepin. The primary end point was pain reduction as measured by the area under the curve (AUC) of the pain scale using data from day 1. Results: Primary end point analysis revealed that the AUC for mouth and throat pain reduction was greater for doxepin (-9.1) than for placebo (-4.7; P < .001). Crossover analysis of patients completing both phases confirmed that patients experienced greater mouth and throat pain reduction with doxepin (intrapatient changes of 4.1 for doxepin-placebo arm and -2.8 for placebo-doxepin arm; P < .001). Doxepin was associated with more stinging or burning, unpleasant taste, and greater drowsiness than the placebo rinse. More patients receiving doxepin expressed a desire to continue treatment than did patients with placebo after completion of each of the randomized phases of the study. Conclusion: A doxepin rinse diminishes OM pain. Further studies are warranted to determine its role in the management of OM.

Original languageEnglish (US)
Pages (from-to)1571-1577
Number of pages7
JournalJournal of Clinical Oncology
Volume32
Issue number15
DOIs
StatePublished - May 20 2014

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Doxepin
Stomatitis
Neck
Radiotherapy
Head
Placebos
Drug Therapy
Pain
Therapeutics
Pharynx
Area Under Curve
Mouth
Arm
Sleep Stages
Head and Neck Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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Doxepin rinse versus placebo in the treatment of acute oral mucositis pain in patients receiving head and neck radiotherapy with or without chemotherapy : A phase III, randomized, double-blind trial (NCCTG-N09C6 [Alliance]). / Leenstra, James L.; Miller, Robert C.; Qin, Rui; Martenson, James A.; Dornfeld, Kenneth J.; Bearden, James D.; Puri, Dev R.; Stella, Philip J.; Mazurczak, Miroslaw A.; Klish, Marie D.; Novotny, Paul J.; Foote, Robert L.; Loprinzi, Charles Lawrence.

In: Journal of Clinical Oncology, Vol. 32, No. 15, 20.05.2014, p. 1571-1577.

Research output: Contribution to journalArticle

Leenstra, James L. ; Miller, Robert C. ; Qin, Rui ; Martenson, James A. ; Dornfeld, Kenneth J. ; Bearden, James D. ; Puri, Dev R. ; Stella, Philip J. ; Mazurczak, Miroslaw A. ; Klish, Marie D. ; Novotny, Paul J. ; Foote, Robert L. ; Loprinzi, Charles Lawrence. / Doxepin rinse versus placebo in the treatment of acute oral mucositis pain in patients receiving head and neck radiotherapy with or without chemotherapy : A phase III, randomized, double-blind trial (NCCTG-N09C6 [Alliance]). In: Journal of Clinical Oncology. 2014 ; Vol. 32, No. 15. pp. 1571-1577.
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abstract = "Purpose: Painful oral mucositis (OM) is a significant toxicity during radiotherapy for head and neck cancers. The aim of this randomized, double-blind, placebo-controlled trial was to test the efficacy of doxepin hydrochloride in the reduction of radiotherapy-induced OM pain. Patients and Methods: In all, 155 patients were randomly allocated to a doxepin oral rinse or a placebo for the treatment of radiotherapy-related OM pain. Patients received a single dose of doxepin or placebo on day 1 and then crossed over to receive the opposite agent on a subsequent day. Pain questionnaires were administered at baseline and at 5, 15, 30, 60, 120, and 240 minutes. Patients were then given the option to continue doxepin. The primary end point was pain reduction as measured by the area under the curve (AUC) of the pain scale using data from day 1. Results: Primary end point analysis revealed that the AUC for mouth and throat pain reduction was greater for doxepin (-9.1) than for placebo (-4.7; P < .001). Crossover analysis of patients completing both phases confirmed that patients experienced greater mouth and throat pain reduction with doxepin (intrapatient changes of 4.1 for doxepin-placebo arm and -2.8 for placebo-doxepin arm; P < .001). Doxepin was associated with more stinging or burning, unpleasant taste, and greater drowsiness than the placebo rinse. More patients receiving doxepin expressed a desire to continue treatment than did patients with placebo after completion of each of the randomized phases of the study. Conclusion: A doxepin rinse diminishes OM pain. Further studies are warranted to determine its role in the management of OM.",
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T1 - Doxepin rinse versus placebo in the treatment of acute oral mucositis pain in patients receiving head and neck radiotherapy with or without chemotherapy

T2 - A phase III, randomized, double-blind trial (NCCTG-N09C6 [Alliance])

AU - Leenstra, James L.

AU - Miller, Robert C.

AU - Qin, Rui

AU - Martenson, James A.

AU - Dornfeld, Kenneth J.

AU - Bearden, James D.

AU - Puri, Dev R.

AU - Stella, Philip J.

AU - Mazurczak, Miroslaw A.

AU - Klish, Marie D.

AU - Novotny, Paul J.

AU - Foote, Robert L.

AU - Loprinzi, Charles Lawrence

PY - 2014/5/20

Y1 - 2014/5/20

N2 - Purpose: Painful oral mucositis (OM) is a significant toxicity during radiotherapy for head and neck cancers. The aim of this randomized, double-blind, placebo-controlled trial was to test the efficacy of doxepin hydrochloride in the reduction of radiotherapy-induced OM pain. Patients and Methods: In all, 155 patients were randomly allocated to a doxepin oral rinse or a placebo for the treatment of radiotherapy-related OM pain. Patients received a single dose of doxepin or placebo on day 1 and then crossed over to receive the opposite agent on a subsequent day. Pain questionnaires were administered at baseline and at 5, 15, 30, 60, 120, and 240 minutes. Patients were then given the option to continue doxepin. The primary end point was pain reduction as measured by the area under the curve (AUC) of the pain scale using data from day 1. Results: Primary end point analysis revealed that the AUC for mouth and throat pain reduction was greater for doxepin (-9.1) than for placebo (-4.7; P < .001). Crossover analysis of patients completing both phases confirmed that patients experienced greater mouth and throat pain reduction with doxepin (intrapatient changes of 4.1 for doxepin-placebo arm and -2.8 for placebo-doxepin arm; P < .001). Doxepin was associated with more stinging or burning, unpleasant taste, and greater drowsiness than the placebo rinse. More patients receiving doxepin expressed a desire to continue treatment than did patients with placebo after completion of each of the randomized phases of the study. Conclusion: A doxepin rinse diminishes OM pain. Further studies are warranted to determine its role in the management of OM.

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