Transdermal buprenorphine for oropharyngeal mucositis-associated pain in patients treated with radiotherapy for head and neck cancer.

Dear Editor: Oropharyngeal mucositis is the most frequent and potentially severe complication of radiotherapy for head and neck cancer. Mucositis-related pain causes impaired food intake and weight loss and generally requires administration of opioids. Transdermal delivery systems offer stable plasma concentration leading to more effective analgesia and fewer toxicity. Buprenorphine transdermal formulation (BPS-TDS; Transtec , Gruenethal GmbH, Aachen, Germany) demonstrated good efficacy with no inhibition of immune system or interference with chemotherapy. We evaluate efficacy of BPS-TDS on mucositis-related oral pain in patients with head and neck cancer treated with radiotherapy. Nineteen patients treated for head and neck cancers were analyzed. All were older than 18 years, with histologic diagnosis of head and neck cancer. All had a performance status of 60 or more following Karnofsky Index. Mucositis, pain level, incidental pain, swallowing impairment, micosis, and weight were assessed weekly. Mucositis was scored following the Common Terminology Criteria for Adverse Events (CTCAE) scale. Oral pain was reported using the Numerical Rating Scale (NRS; 0–10), while dysphagia through the Functional Impairment Scale (FIS). Nutritional support was planned for all patients. In case of weight loss of at least 5% in a week or FIS of 3 or more, enteral nutrition through a feeding tube was started. Buprenorphine was prescribed when pain was still not reduced below NRS 4 after weak opioid assumption. Starting dose was 17.5 mg. Patients treated were 13 males and 6 females. Mean age was 62. Two patients were treated for rynopharyngeal carcinomas, 2 for oral cavity, 8 for oropharyngeal, 5 for hypopharygeal-laringeal cancers, and 2 for nodal metastasis. Treatment plans included extended nodal irradiation up to at least 50 Gy. Smaller volumes received total dose up to 66 Gy. Chemotherapy consisted in weekly cisplatin (40 mg=m) in 10 patients and cetuximab in 2. Seven patients underwent radiotherapy alone. Mean and median weight at the beginning were 70 and 67 kg, respectively. All patients experienced grades 1 and 2 mucositis at a median dose of 20 and 32 Gy, respectively. Fifteen patients (79%) experienced grade 3, at median dose of 44 Gy. NRS value increased with mucosal toxicity: 4 for grade 1, 5 for grade 2, and 7 for grade 3. Micosis was detected in 7 cases, all successfully treated with fluconazole. All patient experienced swallowing functional impairment up to FIS 3. Median weight decreased from 66 kg to 62 kg at the time of buprenorphine prescription, to 60 kg at the end of treatment. Median 8% of total weight loss was detected (range, 5%–15%). Half of patients started buprenorphine with grade 2 mucositis and half with grade 3 at a median dose of 52 Gy (range, 30–66 Gy). After BPS-TDS prescription median NRS decreased from 7 to 2. In half of the patients 17.5 mg were sufficient; in the remaining patients, dose was increased to 35mg. Rescue therapy was prescribed in only 1 patient. Thirtyone percent of patients reported mild constipation or nausea and 6% pruritus. In our limited experience BPS-TDS provided good pain control, with limited dosages and without significant side effects. Transdermal administration is comfortable for these patients with no need for high dose escalation. Patients had significant benefit from therapy: swallowing-related pain, which almost never disappears, was limited to lower NRS scores.