Type of study – A single-centre interventional pilot study without a comparator arm, evaluating the efficacy of transdermal buprenorphine in pain associated with oral mucositis

Study sample and inclusion criteria – 50 oral cancer patients, opioid naive receiving post-operative radiotherapy with or without chemotherapy, with inadequate pain control on non-opioid or topical preparations, with CTCAE mucositis more than grade 2, with pain score more than equal to 4 on visual analogue scale.

Intervention – Transdermal buprenorphine 10 mcg/hr
Dose escalation planned every 72 hours by 5 ug/hr to a maximum dose of 20 ug/hr
Rescue analgesics – Paracetamol 650 mg QID and/or Tramadol 50 mg BD
Pain assessment – Twice weekly pain assessment using Visual analogue scale

Results
The authors state that pain scores improved on both VAS and CTCAE. Adverse effects such as mild sedation, nausea and constipation occurred with a frequency of less than 10 percent with 38 percent of the participants requiring a dose more than 10 mcg/hr.

Methodological critique
The use of buprenorphine in an oral morphine equivalent of 24 mg/day in those with moderate cancer pain only needs to be subject to further scrutiny.
The starting dose of Buprenorphine in opioid naive patients is usually 5 mcg/hr, a starting dose of 10 mcg/hr is considerably higher than recommended.
While the concomitant use of paracetamol and tramadol might be justified (based upon principles of the WHO Step ladder for Cancer pain), this dilutes the argument on the efficaciousness of buprenorphine alone in the study population.
The choice of tramadol over immediate release morphine (though both might be sub-optimal) as rescue analgesia for acute exacerbation of pain episodes also needs to be explained.
Measurement of pain on CTCAE and its differentiation from mucositis severity deserves further scrutiny.
The frequency of pain assessment which is twice a week does not seem in line with the titration schedule which is every 72 hourly, posing a methodological concern about how titration was performed in this cohort.

Summary
While transdermal buprenorphine has been positioned as a safe strong opioid in the opioid naive for moderate to severe pain, its starting dose (as per PCF guidance) remains 5 mcg/hr. Use of rescue analgesia in regular doses also goes against standard and expected use of this terminology. Apart from the absence of an appropriate breakthrough analgesic (given its unique pharmacokinetic profile), there remains the unresolved question of efficacy of morphine in this setting.
While the authors have justified the use of transdermal buprenorphine citing the difficulty in swallowing, they have not taken the fact that both tramadol and paracetamol were also to be administered in the study population via the oral route into consideration. To this specialist, it seems that those who could consume up to six tablets of paracetamol and tramadol, a day could have tolerated crushed immediate release morphine or morphine elixir as well.
The fact that this study comes from a public sector hospital catering mostly to the underprivileged also seems at odds with existing practice and ethical clinical-decision making, which support use of affordable medications first (in this population).
 
Author’s take
The methodological flaws highlighted above require due consideration before transdermal buprenorphine can be positioned as the opioid of choice in the management of moderate mucositis-associated pain. Interestingly, buprenorphine’s kappa receptor partial agonism offers a mechanistically sound but understated rationale for its use in mucositis-associated pain. Had the study been designed to test this specific mechanism, its justification for use in this setting would have had stronger basis.

References

Rastogi, M., Gandhi, A., Khurana, R., Hadi, R., Srivastava, A. K., Verma, R., Mishra, V. K., Soni, S., & Singhal, A. (2026, June 27). Efficacy of transdermal buprenorphine for oral mucositis pain in postop oral cancer patients on radiotherapy with or w/o chemotherapy: A pilot study [Conference presentation]. MASCC/ISOO Annual Meeting 2026, Melbourne, Australia

Disclaimer
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