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

Int J Radiat Oncol Biol Phys. 2020 Feb 1;106(2):320-328. doi: 10.1016/j.ijrobp.2019.10.023. Epub 2019 Oct 25.

Abstract

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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Buccal
  • Adult
  • Aged
  • Analgesics, Opioid / administration & dosage
  • Chemoradiotherapy / adverse effects*
  • Clonidine / administration & dosage*
  • Clonidine / adverse effects
  • Confidence Intervals
  • Deglutition Disorders / etiology
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / radiotherapy*
  • Humans
  • Male
  • Middle Aged
  • Placebos / administration & dosage
  • Radiation-Protective Agents / administration & dosage*
  • Radiation-Protective Agents / adverse effects
  • Radiotherapy Dosage
  • Squamous Cell Carcinoma of Head and Neck / radiotherapy*
  • Stomatitis / etiology
  • Stomatitis / prevention & control*
  • Tablets
  • Young Adult

Substances

  • Analgesics, Opioid
  • Placebos
  • Radiation-Protective Agents
  • Tablets
  • Clonidine