A two-phase study investigating the quality of life benefit of additional 0.5% cocaine mouthwash to institutional standard of care mucositis management in head and neck cancer patients undergoing radiotherapy or chemoradiotherapy.

The intervention was the addition of 0.5% cocaine mouthwash (CMW) to institutional standard of care (SOC) management of mucositis-related pain in head and neck cancer patients undergoing radiotherapy or chemoradiotherapy. This is a single centre, prospective sequential cohort study of eligible consecutive patients that was undertaken at a tertiary hospital in Perth, Western Australia (Sir Charles Gairdner Hospital) between 1 August 2016 and 11 November 2019. Eligible patients had a histologically confirmed head and neck cancer receiving radiotherapy or chemoradiotherapy in the definitive or adjuvant setting. Patients were excluded if they were under 18 years of age, pregnant or breastfeeding, or allergic or intolerant to any of the study treatment intervention. The study was conducted pragmatically and focused on the global impact of the intervention rather than individual patient benefit. The first cohort of patients (the CMW arm) received analgesia prescribed according to the analgesic ladder (see below) guidelines including CMW, and upon completion of the CMW arm, the SOC arm only received medications as per the analgesia guideline without the CMW. The mucositis-related pain management guideline was established following consensus agreement between medical oncology, radiation oncology, palliative care and pain service teams and was disseminated after an educational session. Step 1 of the analgesic ladder focused on topical management. If the patient required topical therapy, all three of the following mouthwashes were provided – (1) benzydamine mouthwash, (2) lignocaine viscous 2% mouthwash, and (3) CMW (in the CMW arm only). Each mouthwash was encouraged to be used regularly four times a day and staggered in use to maximise relief. Step 2 of the analgesic ladder employed the use of short acting analgesia with preference for morphine elixir or hydromorphone elixir at standard doses on a when required basis. Step 3 focused on addition of long-acting analgesia with preference for long-acting oral morphine/ oxycodone or fentanyl patch. Step 2 and step 3 could be initiated simultaneously. The guidelines also recommended routine mouth care and oral hygiene. Patients were not blinded for the intervention. Patients were provided with analgesia prescription whilst undergoing radiotherapy or chemoradiotherapy and for up to 3 months after its completion as required. An a priori decision was not to mandate medication use diary from the patients given the already high burden of care and intervention in this patient group. The decision to enrol patients sequentially in the two arms was pragmatic, based on the required minimum purchase and manufacturing of a batch of the CMW and with consideration of the expiry date of the drug. The SOC arm commenced when the CMW supplies were exhausted. That is, the SOC arm commenced on completion of the CMW arm. Doses for medicines used in the analgesic ladder Benzydamine 0.15% MW 15mL four times a day. Lignocaine viscous 2% 10mL four times a day. Cocaine MW 0.5% 15ml four times a day (in the intervention arm only) Morphine elixir 1mg/mL 5mg hourly on a when required basis Hydromorphone elixir 1mg/mL 1mg hourly on a when required basis Long-acting analgesia (morphine, oxycodone or fentanyl) at standard doses prescribed in routine clinical practice