Prevention & Treatment of Mucositis

Supportive Care in Cancer Therapy Jude Lees Royal Adelaide Hospital Adelaide South Australia

How Common A Problem?

Severe Mucositis - Costs

§ 10% related to adjuvant chemotherapy § 40% related to primary chemotherapy § 80% related to stem cell transplant in using myeloablative conditioning § Patients report mucositis as the most debilitating side effect compared with nausea, vomiting, fatigue & diarrhoea §

100% related to head and neck radiation therapy to fields involving the oral cavity

Mechanisms

•

Significant pain è Opioids (Patient Controlled Analgesia)

• • • • • •

Inability to eat è TPN Oral medications è IV Increased fever & infection Increased length of stay 4-fold increase in mortality higher hospital costs (almost $US43,000 higher in pts with ulcerative mucositis) Sonis ST, Olser G, Fuchs H, et al. JCO. 2001;19:2201-5.

History: Managing Mucositis • • • • • • • • • • • •

Anaesthetics Antimicrobials Antioxidants & vitamins Antiseptics Chemoprotectants “cocktails” Coating agents Corticosteroids Cryotherapy Growth factors Nutritional supplements Others

èlignocaine, benzocaineü èantibiotic mouthwashes èvitamin e, betacarotene èchlorhexidine èamifostine ? è“magic mouthwash” èsucralfate èdexamethasone èice chipsü èGM-csf mouthwash èglutamine ? èallopurinol, leucovorin mouthwash

1

“Salt & Soda” vs. Chlorhexidine vs. “Magic Mouthwash” “Salt and soda” “Magic mouthwash”

= salt+ sod. bicarb + water = lidocaine + Maalaox + diphenhydramine syrup

§ randomised, double-blind trial 200 patients § no significant difference in time to end of signs & symptoms § NO BETTER THAN systematic oral hygiene § use the least costly option

Mucositis § recognised as a major unmet need in supportive care in cancer patients § clinical trials on preventive and treatment agents § MASCC Mucositis Study group very active in guidelines area

Dodd et al, Oral Surg Oral Med Oral Pathol Radiol Endod 2000;90:39-47

2005 Update of MASCC Mucositis Guidelines

MASCC Mucositis Study Group 8 Review groups - Topics •Epidemiology of mucositis, Economics, & Outcome •Pathogenesis •Terminology, Definition & Scales •Growth Factors & Cytokines •Analgesics, Anesthetics, Mucosal Coating Agents & Antimicrobials

Was presented at ISOPP X by Dr Dorothy Keefe, Royal Adelaide Hospital Cancer Centre Chairman: MASCC Mucositis Study group

Changes Since May 2004 •Whole-gut paradigm for mucositis • oral AND alimentary canal

•Alternative & Natural Products, Laser, Ice •Basic Oral Care, Bland Rinses, Good Clinical Practice, Protocol & Education •Anti-Inflammatories, Amifostine

Guideline Classification/Hierarchy Recommendation

guidelines based on Level I or Level II evidence

Suggestion

guidelines based on Level III, Level IV & Level V evidence • Implies panel consensus on the interpretation of this evidence when insufficient evidence on which to base a guideline; implies that:

•new mechanistically-based therapies •better understanding of epidemiology & pathobiology •each group looked at • clinical & preclinical studies

No guideline possible

1) There is little or no evidence regarding the practice in question OR 2) The panel lacks a consensus on the interpretation of existing evidence

2

Oral Care Protocols & Education

Oral Care Protocols & Education

Original Guideline: Suggest use of oral care protocols that include patient education

NEW GUIDELINE:

© MASCC 2004

Suggest performing basic oral care including a soft toothbrush with regular replacement of the toothbrush

Good Clinical Practice •Pain management •Oral assessment & oral care •Dental care: • Pre-treatment, during treatment, follow-up

NEW GUIDELINE: Suggest that protocol development be interdisciplinary •Education should include staff •Quality improvement processes should be used to evaluate protocols and education

Antimicrobial Lozenges •Polymixin, tetracycline, amphotericin B (PTA) •Bacitracin, clotrimazole, gentamicin (BCoG) • Head & Neck RT, adults, prevention • Results: equal to placebo

Previous Guideline:

Insufficient evidence for treatment

NEW GUIDELINE: Recommend against use for prevention

Sucralfate

Nutritional Supplements

RT or CT, adults, prevention

Glutamine

Results: no difference in incidence, severity, duration of oral mucositis & pain

Previous Guideline:

Insufficient evidence for treatment of GI mucositis

Previous Guideline:

NEW GUIDELINE:

No guideline possible

NEW GUIDELINE: • Chemotherapy: No guideline possible • Radiotherapy: Recommend against use for prevention of RT-induced oral mucositis

Suggestion against use of systemic glutamine for prevention

Future Directions: L-glutamine

3

Cytokines and Growth Factors

Cryotherapy

• Previous review GCSF, GM-CSF, KGF & TGF-ß3 seemed promising

Previous Guideline: Cryotherapy is recommended

• many clinical trials 2002 - 2005 • mostly no recommendations either due to insufficient evidence OR toxicity issues

for prevention of mucositis in: • Bolus 5-FU and leucovorin/5-FU

• additional NEGATIVE trials have changed previous recommendation on topical GM-CSF mouthwash è

NEW GUIDELINE: As before plus:

NEW GUIDELINE: - suggest NOT to use

• Suggested for high dose melphalan in BMT

Palifermin for prevention of oral mucositis

Previous Guideline:

• No guideline possible (insufficient evidence)

NEW GUIDELINE: • Patients with haematological malignancies • High dose chemotherapy and TBI with autologous stem cell transplant

• Palifermin 60 µg/kg/day • 3 days prior to conditioning treatment • 3 days post transplant

Level I, Grade A evidence

GM-CSF mouthwash

Mucositis Guidelines •Table

available at: www.mascc.org

•13

papers published in Journal of Supportive Care in Cancer June 2006 •Summary

review paper in final draft

•Education

about the guidelines & promulgation is the biggest hurdle •My

suggestion - pharmacist ideally placed to do this •ISOPP

members - see our website for free copy competition.

Interventions according to Muco sitis Gra de:

Assessment: • •

•

Full oral assessment ( transplant patients will have a dental review during workup) Assess risk factors for developing mucositis Ø Type of chemotherapy Ø Nutritional status Ø Smoking Ø Previous herpes simplex viral infection Ø Underlying disease / myelosuppesssion Daily mucositis grading (WHO grading scale) – see next page

Grade 0

Grade 1

Grade 2

Grade 3

Grade 4

Normal - no mucositis

Mild tissue change s (FOCAL) - white anaemic changes - erythematous pa tches - mucosal thinning

Mild tissue changes (FOCAL) - erythematous / thinning mucosa - sm all ulceration