1. Managing Mucositis Dr Barry Quinn RN Macmillan Consultant Lead Nurse Cancer & Palliative Care EBMT Meeting IET London 5 th October 2012

2. Oral Mucositis OM is defined as inflammation of the mucosa membrane. It is characterised by ulceration, which may result in pain, dysphagia and impairment of the ability to talk. Mucosal injury provides an opportunity for infection to flourish, placing the patient at risk of sepsis and septicaemia (Rubenstein et al, 2004)

3. Damage to Oral Mucosa Patients with oral mucositis may suffer from Severe pain and discomfort 2,3 Inability to eat, drink, swallow, or talk 3 Risk of systemic infections 4 1 Pico JL, et al. Oncologist. 1998;3:446-451; 2 Shea TC, et al. Bone Marrow Transplant. 2003;9:443-452; 3 Bellm LA, et al. Support Care Cancer. 2000;8:33-39; 4 Sonis S. J Support Oncol. 2004;2:21-36. Mucosal BleedingUlceration and Candida Infection 1

4. Incidence rates of mucosal damage 1.Wardley AM et al. Br J Haematol 2000;110:292–299 2. Elting LS, et al. Proceedings from the 17th MASCC/ISOO International Symposium 2005; Abstract #15-097 and oral presentation 3. Kalemkerian GP et al. Lung Cancer 1999;25:175–182 4. Sonis ST et al. Cancer 2004;100(suppl 10):1995–2025 5. Elting LS et al. Cancer 2003;98:1531–1539 6. Blijlevens N et al. Bone Marrow Transplant 2006;37:S24–S25 Oral and/or GI 37**11**Solid tumours Myelosuppressive chemotherapy 5 Oral87*44*Multiple myeloma, NHL High-dose melphalan, BEAM 6 GINo data42*NSCLCChemoradiotherapy 3 Oral GI No data 53* 39* GI malignancy Radiotherapy and 5-FU and CPT-11 4 Oral and/or GI 88–98*60–77* Head and neck cancer Radiotherapy  chemotherapy 2 Oral99*67–98* Solid and haematological Conditioning for HSCT 1 Mucosal damage All grades Grade 3–4 MalignancyTreatment Incidence *% of patients; **% of cycles

5. 1. Adapted from Bellm LA et al, Support Care Cancer 2000;8:33–9 Most debilitating side effects 45 Respondents (%) 40 35 30 25 20 15 10 5 0 Oral mucositis Nausea and vomiting Weakness and lethargy Diarrhoea Oral mucositis: rated by some patients as the worst complication of high-dose chemotherapy for HSCT 1

6. Treatment & Disease Hepatic toxicity Pain Infertility Infections Fatigue New roles Loss of privacy Nausea and vomiting DiarrhoeaConstipation Oral damage Weight loss <Nutrition Body changes Relapse Renal Complications Neurological complications Pulmonary changes Cardiac toxicity Urological problems Secondary malignancy Thrombocytopenia Anaemia Spiritual distress Alopecia Leucopenia Isolation Lack of control Sleep disturbance Drug reactions Fluid & Electrolyte imbalance Sexual changes GI disturbance Bleeding disorders CataractsSkin toxicity

7. A Neglected Task Despite its acknowledged importance, oral care is one of the first things to be set aside when workloads are excessive (McGuire 2003)

8. Mucosal Damage: a Complex Biological Process Adapted from Sonis ST. Cancer. 2004;100(suppl 10):1995-2025.

9. High Turnover Rate of Mucosal Cells Makes Them Susceptible to Damage from Cytotoxic Therapy Normal mucosa provides an effective protective barrier High epithelial turnover Reduced turnover Reduced epithelial turnover leads to mucosal breakdown Mucosal injury DNA damage NonDNA damage Generation of ROS Mucosa becomes susceptible to injury Adapted from Sonis ST. Nat Rev. 2004;4:277-284. ROS = reactive oxygen species

10. Background Objective to form an expert group that changes the approach to and management of OM

11. UKOMiC Group Dr Barry Quinn Nurse Consultant/Lead Cancer Nurse (Chair) Michelle Davies Research Nurse Haematology Jeff Horn Clinical Nurse Specialist (CNS) Haematology Emma Riley Macmillan Dental Nurse Dr Jenny Treleaven Consultant Haematologist David Houghton Senior Pharmacist Annette Beasley CNS Head and Neck Dr Catherine McGowan Palliative Care Consultant Maureen Thomson Consultant Radiographer Lorraine Fulman Information and Support Radiographer, Head and Neck and Gynaecology Kathleen Mais Nurse Clinician, Head and Neck Oncology Professor Petra Feyer Consultant Clinical Oncologist Sonja Hoy CNS Head, Neck and Thyroid Cancer Frances Campbell CNS Head and Neck Cancer

12. Background Oral problems, including oral mucositis (OM), can be a significant health burden for the individual. They also make substantial demands on health care resources. A multi-professional group of UK oral care experts working in cancer and palliative care has drawn on their expertise and the most up-to- date evidence to develop guidance and support on the assessment, care, prevention and treatment of oral problems secondary to disease and treatments.

13. Guidance This guidance has been developed for all health care professionals involved in the care and treatment of cancer patients. It is anticipated that it can be adapted to other clinical settings, including palliative and terminal care, and other specialist areas such as gerontology.

14. Care of the Oral Cavity All patients undergoing high-dose chemotherapy or HSCT procedure, and all head and neck cancer patients, should ideally be referred for dental assessment prior to commencing treatment.

15. Oral Assessment

16. Assessment of Oral Mucositis 1 World Health Organization. Handbook for reporting results of cancer treatment. 1979;pp. 15-22. Scale Mucositis Grade 01234 WHO Oral Toxicity Scale 1 NoneSoreness and erythema Erythema, ulcers, patient can swallow solid diet Ulcers, extensive erythema, patient cannot swallow solid diet Mucositis to extent that alimentation not possible WHO = World Health Organization

17. Prevention of therapy induced OM The choice of prevention regimens for mucositis will depend on the perceived risk of mucositis. Compliance with the prevention measures and good oral hygiene will minimise the risk of subsequent issues with mucositis.

18. Prevention of therapy induced OM

20. Anti-Infective Prophylaxis As well as good oral hygiene, patients receiving chemotherapy for haematological cancers may be prescribed antifungal and antiviral treatments to prevent infections. Infection prophylaxis for head and neck cancer patients is only required if the patient is known to be at risk of infection due to co-morbidity factors. Antifungal prophylaxis should be given to patients receiving high- dose steroids (the equivalent of at least 15 mg of prednisolone per day for at least one week), and may include 50 mg oral fluconazole once daily. High-risk patients, including those undergoing HSCT, should also receive an antifungal agent; this may include fluconazole, itraconazole or posaconazole (the choice of drug will be dependent on local guidance). Antiviral prophylaxis may comprise 200 mg aciclovir three times a day orally (or according to local guidance).

21. Treatment of Therapy-Induced Mucositis Grade 1 or 2 Mucositis Ensure oral hygiene is adequate. Consider increasing the frequency of saline rinses. Closely monitor nutritional status & refer to dietician. Provide simple analgesia, which may include soluble paracetamol 1 g four times daily. It should be remembered that paracetamol may mask fever. Escalate to soluble co-codamol 30/500 if required. The use of NSAIDs is contraindicated due to the risk of bleeding and renal impairment (Keefe et al., 2007). Consider benzydamine 0.15% oral solution (Difflam®), 10 ml rinsed around the mouth and spat out. Repeat between every 1.5 to 3 hours, as required. However, this may be poorly tolerated in patients with severe mucositis. Consider increasing folinic acid rescue for methotrexate-induced mucositis. Check to see if the patient has evidence of oral infection and if so ensure an anti-infective agent is prescribed. Consider Caphosol® (4–10 times a day) to prevent grade 1 and 2 OM becoming more severe.

22. Treatment of Therapy-Induced Mucositis Grade 3 or 4 Mucositis In addition to the recommendations for grade 1 and 2 OM, the following should be considered: Use of stronger analgesia, including Oxynorm®, Sevredol® and Oramorph® (Oramorph® may sting mucosa due to its alcohol base). If patients continue to suffer from pain from mucositis, consider - fentanyl patches, patient ‑ controlled analgesia or a syringe driver (seek advice from the acute pain team or the palliative care service). Laxative medications should be prescribed to prevent constipation and associated nausea. Ensure intravenous and/or enteral hydration and feeding is prescribed, as oral intake may be reduced. Consider Caphosol®. Consider applying a coating protectant, e.g. Gelclair®, MuGard®, Episil®. The product should be rinsed around the mouth to form a protective layer over the sore areas, and generally applied 1 hour before eating.

23. Treatment of Therapy-Induced Mucositis

24. Reference guides

25. www.ukomic.co.uk

26. Conclusion “My mouth became ulcerated and I could not swallow my own saliva. Every day of chemo brought some new horrifying change to my body” (Liz)