A case series of patients with head and neck cancer undergoing curative-intent chemoradiation receiving low dose transdermal buprenorphine for pain
Case Series | Management in Palliative Medicine and Palliative Care

A case series of patients with head and neck cancer undergoing curative-intent chemoradiation receiving low dose transdermal buprenorphine for pain

Kevin Dyer1, Mara Feingold-Link1,2, Dana Guyer1,2 ORCID logo

1Department of Medicine, Division of Geriatrics and Palliative Medicine, Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI, USA; 2HopeHealth, Providence, RI, USA

Contributions: (I) Conception and design: All authors; (II) Administrative support: All authors; (III) Provision of study materials or patients: All authors; (IV) Collection and assembly of data: All authors; (V) Data analysis and interpretation: All authors; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Correspondence to: Dana Guyer, MD. Department of Medicine, Division of Geriatrics and Palliative Medicine, Warren Alpert Medical School of Brown University, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, USA; HopeHealth, Providence, RI, USA. Email: dana.guyer@brownhealth.org.

Background: Buprenorphine is a semisynthetic partial µ-opioid receptor agonist used for opioid use disorder and increasingly for cancer-related pain. Transdermal buprenorphine (TDB) is effective for both nociceptive and neuropathic pain and may be particularly advantageous in patients with head and neck cancer (HNC) due to its pharmacologic profile and non-oral route of administration. Existing literature evaluates the efficacy of high dose TDB (>30 µg/h) in symptom management and demonstrates equivocal effectiveness to morphine. In the United States, TDB patches are only available in 5, 7.5, 10, 15, and 20 µg/h patches with a max dose of 20 µg/h approved by the Food and Drug Administration. Data on low-dose TDB for HNC-related pain and treatment-associated toxicities, including mucositis, are limited.

Case Description: We performed a single center, retrospective review of nine patients with HNC who started or completed treatment between 2024 to 2025 All patients were treated in the HNC multidisciplinary clinic, which includes medical oncology, radiation oncology, otolaryngology, nutrition, navigation, and a palliative care physician at an academic hospital. Pain was treated primarily with TDB at varying doses, with adjuvant analgesics as needed, and patients were followed longitudinally during the course of their treatment. Analgesic regimens were adjusted as anticipated complications such as mucositis and odynophagia developed. While some patients required short-term full agonist opioids, most required fewer than 30 oral morphine equivalents daily in addition to their TDB. All patients were successfully weaned off full agonist opioids during post-treatment follow-up. Most patients completed their treatments with minimal interruptions. Instances of incomplete treatment included extenuating social circumstances, chemotherapy-related acute kidney injury, and dose-limiting cytopenias.

Conclusions: In our clinical experience, low dose TDB demonstrated efficacy in managing pain and limiting the need for full agonist opioids, and patients were able to achieve complete weaning of all full agonist opioids post-treatment. This study shows that low dose TDB can be a viable analgesic option for pain related to HNC and treatment sequelae while reducing total exposure to full agonist opioids, which makes it an ideal choice for patients who may have a history of substance use disorder.

Keywords: Case series; transdermal buprenorphine (TDB); head and neck cancer (HNC); pain

Submitted Jan 10, 2026. Accepted for publication Mar 26, 2026. Published online May 26, 2026.

doi: 10.21037/apm-2026-1-0008

Highlight box

Key findings

• Low dose transdermal buprenorphine (TDB) (<30 µg/h) can provide adequate pain control in patients being treated for head and neck cancer (HNC).

• Pain management with only TDB (<30 µg /h) can prevent the need for full agonist opioids.

• Patients did not have treatment interruptions due to poor pain control when managed with TDB.

What is known and what is new?

• TDB at high doses (>30 µg/h) has equal efficacy as morphine when treating cancer-related pain

• Buprenorphine has a better safety profile compared to full agonist opioids

• Our clinical experience suggests that low dose TDB is an effective analgesic option in HNC patients with nociceptive and neuropathic pain. Our cohort suggests that a low dose regimen may also decrease the need for and facilitate the weaning of full agonist opioids.

What is the implication, and what should change now?

• Low dose TDB patches available in the U.S. can still provide adequate analgesia to patients undergoing treatment for HNC without an observed increase in pain-related treatment interruptions.

• Low dose TDB should be considered a routine analgesic option when treating patients with HNC pain.

Introduction

There was estimated to be 60,000 new cases of cancers of the oral cavity and pharynx and 13,000 new cases of laryngeal cancer in 2025 (1). Head and neck cancer (HNC) is associated with significant morbidity, both from the cancer itself and the intensive treatment patients undergo to achieve cure. HNC patients experience the highest prevalence of pain in patients with cancer (2). HNC-associated pain includes both nociceptive and neuropathic components (3-6), making it especially difficult to treat. Among the many physical and psychosocial complaints that HNC patients are referred for supportive care, pain is among the most distressing (7).

A major cause of pain in this population is oral mucositis related to radiation, chemotherapy, or combined chemoradiation (3,4,8-10). Pain from oral mucositis can lead to complications such as treatment interruption, limited oral intake requiring feeding tube placement, decreased quality of life, and the need for opioid-based analgesia (3,10). Many HNC patients continue to use opioid medications for months after treatment has finished (11). One study found that 7.2% of HNC patients who had undergone curative-intent treatment were using opioids at one year post-treatment, most of them for pain related to their cancer treatment (12). Opioids have a number of well-known side effects, including constipation, nausea, sedation, respiratory depression (9,13,14), and tolerance. Finding pain control options that minimize the risk of these additional side effects is critical in a population of patients already experiencing significant morbidity from their cancer and its treatment. Moreover, major risk factors for developing HNC include tobacco and alcohol use, so any medication that can lead to issues with addiction can be problematic in a population with a high degree of substance use disorder (SUD) (15).

Buprenorphine is an opioid with a unique pharmacologic profile and unique benefits in the clinical setting (16-18). Compared to pure µ-opioid receptor agonists, it has been found to be as effective for pain and to cause less constipation, less respiratory depression and less tolerance (14,16-19). Unlike other opioids, which can cause hyperalgesia, buprenorphine has anti-hyperalgesia effects (20). Despite misconceptions to the contrary, there does not appear to be a ceiling on its analgesic effects (17,18). Buprenorphine is also effective for neuropathic pain unlike pure µ-opioid receptor agonists, can be used with other opioids for breakthrough pain, and is one of the safest opioids in renal failure (16,17,21). In a 2018 study on patients with cancer-related pain, transdermal buprenorphine (TDB) was found to have similar efficacy, greater compliance, and less toxicity when compared to oral morphine (22). Buprenorphine offers a promising option for pain control in the HNC population, since these patients experience such a high side effect burden. The transdermal formulation of buprenorphine may be particularly helpful in HNC patients since oral administration of medications can be limited due to mucositis (23).

While TDB has been shown to be effective in patients with mucositis-related pain after stem cell transplant (19) and HNC patients treated with radiotherapy and chemoradiation, there remains a paucity of data on the use of TDB for mucositis-related pain in HNC patients undergoing curative-intent treatment, specifically with the low-dose 7-day buprenorphine transdermal patch formulation (5, 7.5, 10, 15, and 20 µg/h) (19,24,25). Here, we present nine patients treated at an academic associated cancer center who used low-dose TDB for mucositis-related pain during their chemoradiation treatment for HNC. We present this article in accordance with the AME Case Series reporting checklist (available at https://apm.amegroups.com/article/view/10.21037/apm-2026-1-0008/rc).

Case presentation

We present a case series with a cohort of nine patients diagnosed with HNC of various subtypes that were treated in the HNC multidisciplinary clinic, which includes medical oncology, radiation oncology, otolaryngology, nutrition, navigation, and a palliative care physician in an academic associated cancer center. Through a retrospective, single-center chart review, we followed patients’ analgesic regimens before, during, and after completion of disease-directed therapies. This data was obtained primarily through review of palliative care, oncology, and radiation oncology provider notes and relevant clinical imaging. In addition, we collected general demographic data, history of substance use, and three month post-treatment positron emission tomography (PET) scan results when available. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent for publication of this case series was not obtained from the patients or the relatives given only de-identified data are presented in this article. Table 1 shows demographic and diagnostic data for each patient. Seven out of nine patients had a history of substance use; tobacco was the most common substance used. All patients were diagnosed with squamous cell carcinoma of various locations including tonsil, base of tongue, buccal mucosa, or larynx. The majority of patients presented with metastatic disease to the cervical chain lymph nodes, consistent with locally advanced disease. Patients were planned to be treated with cisplatin (high or low dose) and 70 Gy radiation delivered in 35 fractions. Alterations to treatment plans occurred due to various disease- or patient-specific factors, toxicities (renal dysfunction, cytopenia), and social circumstances. Of note, all patients included in this case series developed varying degrees of mucositis severity, ranging from grade 1 to grade 4. Table 2 shows analgesic regimens before, during, and after treatment. Patients were all treated with TDB for pain at varying doses, with adjuvant analgesics as needed. Adjuvant therapies included acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), gabapentin, and full agonist opioids for breakthrough pain. Full agonist opioids that were used included oral oxycodone immediate release (IR), oxycodone oral solution, morphine (both IR and extended-release formulations), and hydromorphone. Patients’ analgesic regimens were titrated as needed based on their symptoms and treatment course. Most patients had a three month post-treatment PET scan that demonstrated resolution of their malignancy, although not all patients had completed this test. Most patients completed treatment without the use of full agonist agents or required a total of <30 mg oral morphine equivalents (OME) daily. At the most recent post-treatment follow-up visit documented, eight of nine patients were no longer using any opioid medications, and one patient remained on 10 µg/h TDB.

Table 1

Patient demographics, cancer diagnosis, cancer treatment, need for PEG tube, post-treatment PET scan, and history of substance use

Patient No. Age, years Sex Primary diagnosis Treatment PEG tube required PET scan 3 months post-treatment History of substance use
1 56 M SCC of tongue base Cisplatin: 7 cycles; radiation therapy: 35 fractions Yes Pending Tobacco, alcohol, marijuana
2 82 M SCC of the cheek Carboplatin: 6 cycles; radiation therapy: 30 fractions No Pending Tobacco
3 68 M Laryngeal SCC Radiation therapy: 32 fractions No Residual uptake consistent with post-radiation inflammation Alcohol use, opioid use, tobacco
4 43 M SCC of tongue base with lymph node mets Cisplatin: 7 cycles; radiation therapy: 35 fractions No Resolution of neoplasm s/p salvage neck dissection of residual LN, pathology negative for residual disease Tobacco
5 65 M SCC of tongue base with lymph node mets Carboplatin/paclitaxel/cetuximab: 6 cycles carboplatin/paclitaxel: 7 cycles; radiation therapy: 35 fractions No Pending None
6 68 M SCC of tonsil Cisplatin: 7 cycles; radiation therapy: 35 fractions No Resolution of disease Tobacco, marijuana, and alcohol
7 67 M Papillary squamous cell carcinoma of hypopharynx Cisplatin: 7 cycles; radiation therapy: 35 fractions Yes Pending Tobacco
8 64 M SCC of the right tongue base with lymph node mets Cisplatin: 7 cycles; radiation therapy: 35 fractions No Resolution of disease None
9 54 M SCC of right tongue base with lymph node mets High dose cisplatin (platinol): 3 cycles; radiation therapy: 35 fractions Yes Resolution of primary disease site, residual LN uptake favored to be inflammatory changes Tobacco

LN, lymph node; M, male; mets, metastatic disease; PEG, percutaneous endoscopic gastrostomy; PET, positron emission tomography; s/p, status post; SCC, squamous cell carcinoma.

Table 2

Patient analgesic regimen before, during, and after cancer treatment

Patient No. Pain regimen: pre-treatment Pain regimen: during treatment Completion of treatment? Treatment interruptions Post treatment pain medications
1 None TDB max dose 20 mcg/h Partial 35/35 RT fractions 5/7 cycles of cisplatin Weaned off all opioids
Oral hydromorphone 2 mg, utilized 1–2 doses/week
2 Gabapentin TDB max dose: 10 mcg Yes None Hydromorphone 2 mg BID for trismus exercises
Oral hydromorphone max dose 4 mg BID
3 Gabapentin TDB max dose: 20 mcg/h Yes None Weaned off all opioids
Oral morphine IR 15 mg BID
4 None Acetaminophen, celecoxib, gabapentin (900 mg TID) Yes None Weaned off all opioids
Oral hydromorphone 8–16 mg q4h as needed (taken every 4 hours)
TDB max dose 30 mcg/h (stopped)
Oral morphine ER 60 mg TID
5 Acetaminophen and NSAIDs Acetaminophen and NSAIDs, TDB: max dose 5 mcg/h Yes None Weaned off all opioids
Gabapentin 300 mg TID (did not take)
6 Alprazolam and acetaminophen Gabapentin 300 mg BID Yes None Weaned off all opioids
TDB max dose 20 mcg/h
Oral oxycodone IR 5 mg q4h as needed (utilized up to 4 doses per week)
7 Oxycodone 5 mg q6h as needed TDB max dose 10 mcg/h Yes None Continues with TDB 10 mcg
Oral oxycodone 5 mg q6h as needed (utilized 1–2 doses per day)
8 None TDB max dose 20 mcg/h Yes None Weaned off all opioids
Oral hydromorphone 2 mg q6h as needed (not used)
9 None Oral morphine IR 15 mg q4h as needed (not utilized daily) Yes None Weaned off all opioids
TDB max dose 20 mcg/h
Gabapentin 300 mg nightly celecoxib 200 mg BID
Acetaminophen 1 gram TID

Table also shows treatment interruptions if applicable. BID, twice per day; ER, extended release; IR, immediate release; NSAIDs, nonsteroidal anti-inflammatory drugs; q4h, every 4 hours; q6h, every 6 hours; RT, radiation therapy; TDB, buprenorphine; TID, three times per day.

Discussion

Effective pain management is essential for patients with HNC receiving curative-intent chemoradiation so that patients can maintain treatment intensity and minimize treatment interruptions, leading to more effective treatment response. The most significant side effect of HNC treatment is oral mucositis, which can be both incredibly painful and a challenging symptom to effectively manage. Adequate management of mucositis improves quality of life as well as decreases the need for tube feeds, aspiration events, and recurrent hospitalizations (8,9). Furthermore, the maintenance of oral intake during treatment prevents disuse atrophy of the oral mucosa and improves post-treatment oral pain that is evoked by foods or liquids of varying temperature and acidity (9). Significant neuropathic pain is prominent in patients with HNC both during and after treatment and is poorly managed by opioids. Gabapenintoids, tricyclic antidepressants and serotonin-norepinerphrine re-uptake inhibitors may confer some benefit and potentially decrease total opioid usage, but rarely provide complete pain relief (11,26).

Historically, most patients undergoing chemoradiation for HNC have been managed with pure µ-opioid receptor agonists, and the use of these medications remains central to the management of cancer-related pain. However, there are drawbacks to this strategy. The high side effect burden associated with full µ-opioid agonists includes dose-dependent respiratory depression, tolerance, hyperalgesia, cognitive clouding, myoclonus, constipation, pruritus, nausea, and long-term safety concerns. HNC patients often require prolonged courses of opioids during an extended duration of treatment, which increases patients’ risk for chronic opioid use and physiologic dependence. Furthermore, a common risk factor for HNC includes tobacco and alcohol use. SUD is also a noted comorbidity for many patients with HNC. In addition, SUD is often coupled with psychiatric disorders, increasing the risk for addiction, and therefore, particular care is encouraged in choosing analgesic regimens to minimize risk for SUD recurrence or exacerbation (11).

Buprenorphine, a semi-synthetic opioid, offers a mechanistically distinct opioid alternative with several pharmacologic properties that may mitigate these risks. As a high-affinity, partial µ-agonist and κ-antagonist, buprenorphine produces potent analgesia while exhibiting a ceiling effect on respiratory depression, making it safer than full µ-opioid agonists. Its high affinity for opioid receptors results in prolonged analgesic duration and reduced fluctuation in serum levels, leading to consistent pain relief. κ-receptor antagonism attenuates opioid-induced hyperalgesia, dysphoria, tolerance, and a lower risk of misuse relative to other opioids (18). Additionally, buprenorphine has a more pronounced effect on neuropathic pain and confers less risk of hyperalgesia secondary to central sensitization (17,27,28).

Current literature suggests that high dose TDB can reduce total daily OME and have fewer side effects that are typically associated with full agonist opioids, and our study suggests similar efficacy with low dose TDB (19,22). Additional trials have also shown improvements in sleep, mental well-being, and gastrointestinal tolerance (29). All nine patients in our series were prescribed a full agonist opioid for breakthrough pain, however the frequency of use and dose were mitigated by the efficacy of the TDB. Except for two patients, all were weaned off opioids post-treatment, which is an important achievement to allow patients to move forward after cancer treatment and live without opioids. Of note, Table 2 shows that patient number 7 self-reported using oxycodone one to two times per day prior to diagnosis of HNC for chronic back pain. There was no reported dose escalation during treatment and was only on a 10 µg/h patch at his most recent post-treatment evaluation. Patient number 2 used oral hydromorphone 2–4 mg twice per day only when performing trismus exercises during treatment and post-treatment. In addition, patient 8 was also prescribed oral hydromorphone but on multiple outpatient clinic notes, the prescription was never utilized. Patient number four reported using the as needed 8–16 mg of oral hydromorphone every four hours (daily OME 240–480) depending on level of pain, and TDB 30 mcg/h that was ultimately transitioned to morphine 60 mg extended release three times a day in the final week of radiation. Despite an OME of more than 500 mg daily at the end of treatment, he was weaned completely off opioids within three months of completing chemoradiation.

Substance use, specifically alcohol and nicotine, are known risk factors for the development of HNC. A recent cross-sectional study showed the prevalence of SUD amongst cancer survivors between 2015 to 2020 was approximately 4% and HNC patients had the highest prevalence at 9%. Furthermore, 18% of respondents that were diagnosed with cancer in the last 12 months with active substance abuse were diagnosed with HNC (30). Seven of nine patients had a positive social history for prior or current substance use (tobacco, alcohol, marijuana, opioids) with 100% tobacco use rate. Patients receiving radiation therapy for HNC are at risk for chronic opioid use and this risk is further increased by history of alcohol use and pre-treatment opioid use (11). As previously noted, nearly all patients in this case series were weaned off opioids after treatment. Our clinical experience and reflection suggest that low dose TDB may help prevent chronic opioid use and carries a low risk of difficulty weaning patients off opioids, especially those with a history of substance use.

Due to its favorable profile, the palliative care team at our institution has preferentially been using buprenorphine when possible to treat cancer-related pain. In our study, all 9 patients were treated with TDB in conjunction with multimodal therapies and full agonist opioids when indicated. TDB dosing ranged from 5 to 30 µg/h. While receiving concurrent chemotherapy and radiation treatment, eight of nine patients completed treatment without interruptions. Patient number 1 completed five of seven cycles of chemotherapy due to gastrointestinal toxicities, but pain was not a factor in the decision to skip the final two chemotherapy cycles.

Collectively, our case series demonstrates the successful clinical application of TDB and supports its emerging role as a safe, effective, and adaptable analgesic for the complex pain syndromes associated with HNC. Our experience suggests that TDB is an appropriate and feasible first line opioid analgesic for patients receiving curative-intent chemoradiation for HNC. The particular beneficial properties include its transdermal application, efficacy in treating nociceptive and neuropathic pain, and favorable pharmacokinetics which allow for aggressive and safe up-titration as symptoms progress during treatment. While current literature has evaluated high dose (>30 µg/h) regimens (24), our cohort indicates a benefit of low dose buprenorphine (5 to 30 µg/h) in symptom management for patients being treated in the United States, where high dose preparations are unavailable.

There are several important limitations of this study. This was a single-center and retrospective study that had a limited sample size of nine. Patients’ responses to buprenorphine and need for adjunctive medications such as full agonists were recorded based on chart review without a standardized pain scale across all patients. Inherent to chart review, clinical reasoning surrounding disease directed therapies and interruptions are limited by the quality and detail of clinical documentation. The low dose TDB patch formulation (5, 7.5, 10, 15, and 20 µg/h) are the only TDB options available in the United States. Therefore, ongoing research is required to further evaluate the role of low dose TDB for pain management in patients undergoing treatment for HNC. Our clinical experience described above demonstrated a high rate of success of total opioid weaning after treatment completion, however, further exploration of weaning duration with TDB would be beneficial as well. Future studies should consist of a larger sample size, standardized assessment of pain and opioid related side effects, and ongoing monitoring of pain management needs after completion of treatment.

Conclusions

Most patients receiving concurrent chemoradiation for treatment of HNC will experience both nociceptive and neuropathic pain during treatment that causes a significant burden on quality of life and can lead to treatment intolerance and possibly negatively affect treatment efficacy. Low dose TDB is a unique semisynthetic partial agonist opioid that can provide analgesia for both types of pain and potentially improve treatment adherence with lower risk of opioid-related side effects. When used with full agonist opioids, it can limit the total daily OME patients require. With an ideal safety profile and pharmacokinetics, it is the safer opioid and can facilitate easier weaning of all opioid pain medications after treatment completion. Although most literature has focused on high dose regimens, the low dose patches available in the U.S. can be an effective analgesic option for patients.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the AME Case Series reporting checklist. Available at https://apm.amegroups.com/article/view/10.21037/apm-2026-1-0008/rc

Peer Review File: Available at https://apm.amegroups.com/article/view/10.21037/apm-2026-1-0008/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://apm.amegroups.com/article/view/10.21037/apm-2026-1-0008/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent for publication of this case series was not obtained from the patients or the relatives given only de-identified data are presented in this article.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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Cite this article as: Dyer K, Feingold-Link M, Guyer D. A case series of patients with head and neck cancer undergoing curative-intent chemoradiation receiving low dose transdermal buprenorphine for pain. Ann Palliat Med 2026;15(3):41. doi: 10.21037/apm-2026-1-0008

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