What prophylactic measures should be used to prevent stomatitis in patients undergoing chemotherapy, head‑and‑neck radiation, hematopoietic stem‑cell transplantation, or who are severely immunosuppressed?

Prophylaxis for Stomatitis in Cancer Patients

Use oral care protocols with basic oral hygiene measures across all cancer treatment modalities, and add specific interventions based on the treatment type: oral cryotherapy for bolus 5-fluorouracil or high-dose melphalan, low-level laser therapy for HSCT conditioning, benzydamine mouthwash for moderate-dose head-and-neck radiation (up to 50 Gy without chemotherapy), and palifermin for autologous HSCT with TBI-based regimens. 1, 2

Universal Preventive Measures for All Patients

Basic oral care protocols should be implemented for all cancer patients regardless of treatment modality:

• Brush teeth twice daily with a soft toothbrush using gentle technique 1, 3
• Rinse with alcohol-free mouthwash at least 4 times daily 1, 4
• Maintain adequate hydration throughout the day to keep oral mucosa moist 5
• Avoid crunchy, spicy, acidic, or hot foods and drinks 5

These measures have Level III evidence supporting their use across all age groups and cancer treatment modalities 1, 3. The evidence base is modest but consistent, and these interventions carry minimal risk while providing foundational mucosal protection.

Treatment-Specific Prophylaxis

For Bolus 5-Fluorouracil Chemotherapy

Administer 30 minutes of oral cryotherapy (ice chips) during the infusion:

• This intervention has Level II evidence and is strongly recommended 1
• The mechanism involves vasoconstriction that reduces drug delivery to oral mucosa during peak plasma concentrations
• Timing is critical—cryotherapy must be administered during the actual bolus infusion period 1

For Hematopoietic Stem Cell Transplantation (HSCT)

Two evidence-based prophylactic options exist:

Low-level laser therapy (LLLT) is recommended for patients receiving high-dose chemotherapy conditioning with or without total body irradiation:

• Use wavelength at 650 nm, power of 40 mW 1
• Treat each square centimeter with tissue energy dose of 2 J/cm² 1
• This has Level II evidence supporting its use 1
• Recent meta-analyses confirm LLLT significantly reduces severe mucositis incidence 6, 7

Palifermin (recombinant human keratinocyte growth factor-1) is FDA-approved specifically for autologous HSCT with TBI-based preparative regimens:

• Administer 60 mcg/kg/day IV for 3 consecutive days before conditioning therapy 2
• Administer 60 mcg/kg/day IV for 3 consecutive days after stem cell infusion 2
• Critical timing requirement: Do not administer within 24 hours of chemotherapy, as this increases epithelial cell sensitivity and paradoxically worsens mucositis 2
• In clinical trials, palifermin reduced median days of severe (WHO Grade 3/4) mucositis from 9 days to 3 days 2
• Important limitation: Palifermin showed lack of efficacy with high-dose melphalan-only conditioning regimens (without TBI) 2

For melphalan-based HSCT conditioning specifically:

• Oral cryotherapy is effective and should be used 6, 7
• Multiple RCTs demonstrate significant reduction in severe mucositis incidence (RR = 0.52,95% CI = 0.27-0.99) 6
• Cryotherapy also reduces TPN duration and hospital length of stay 6
• This is particularly effective with alkylating agents like melphalan that have short plasma half-lives 7

For Head and Neck Radiation Therapy

Benzydamine mouthwash 0.15% is recommended for moderate-dose radiation (up to 50 Gy) without concurrent chemotherapy:

• This has Level I evidence supporting its use 1
• Use as a rinse multiple times daily throughout radiation treatment
• Critical limitation: Evidence only supports use up to 50 Gy; efficacy at higher doses or with concurrent chemotherapy is not established 1

Interventions Specifically NOT Recommended for Prevention

The following should NOT be used, as strong evidence demonstrates lack of efficacy or potential harm:

Strongly Recommended Against (Level I-II Evidence):

• Sucralfate mouthwash for any cancer treatment modality 1
• Iseganan antimicrobial mouthwash for HSCT or head-and-neck radiation 1
• Intravenous glutamine for HSCT conditioning 1
• PTA (polymyxin, tobramycin, amphotericin B) lozenges for head-and-neck radiation 1
• BCoG (bacitracin, clotrimazole, gentamicin) lozenges for head-and-neck radiation 1

Suggested Against (Level II-III Evidence):

• Chlorhexidine mouthwash for head-and-neck radiation—despite its antimicrobial properties, it does not prevent mucositis and may cause mucosal irritation 1, 3
• GM-CSF mouthwash for HSCT 1
• Systemic pilocarpine for any indication 1
• Systemic pentoxifylline for bone marrow transplantation 1
• Misoprostol mouthwash for head-and-neck radiation 1

Common Pitfalls to Avoid

Do not confuse prevention with treatment: Many agents studied for mucositis treatment (such as morphine mouthwash or doxepin mouthwash) have no role in prevention and should only be used once mucositis develops 5, 4.

Avoid alcohol-containing mouthwashes: These aggravate oral mucosa and worsen mucositis 4.

Do not use "magic mouthwash" for prevention: Despite widespread use, magic mouthwash (diphenhydramine-lidocaine-antacid combinations) has no evidence supporting prophylactic efficacy and should only be considered for symptomatic relief once mucositis occurs 5, 8.

Timing matters with palifermin: The 24-hour separation from chemotherapy is critical—administering palifermin too close to chemotherapy can increase mucositis severity rather than prevent it 2.

Ensure proper dental evaluation before starting therapy: Address existing dental disease and ill-fitting appliances before initiating cancer treatment, as these can significantly worsen mucositis 4.