GM-CSF Mouthwash for Preventing and Treating Mucositis in Patients Undergoing Radiation Therapy for Head and Neck Cancer

Management of Mucositis With GM-CSF (Sargramostim) Mouthwash Study Protocol

GM-CSF may protect normal cells from the side effects, such as mucositis, of radiation therapy and may help damaged tissue heal faster after radiation therapy. This randomized clinical trial is studying how well GM-CSF works in preventing and treating mucositis in patients who are undergoing radiation therapy for head and neck cancer.

OBJECTIVES:

Primary

• Compare the incidence of radiotherapy (RT)-induced oral mucositis of any grade, using the Radiation Therapy Oncology Group Acute Radiation Morbidity Scoring Criteria (RTOG ARMSC)-Mucous Membrane, in patients treated with 1 of 2 mouthwashes (sargramostim [GM-CSF] or salt and soda). (prevention portion of the study)
• Compare the effectiveness of the 2 mouthwashes in treating oral mucositis as defined by the incidence of RTOG ARMSC-Mucous Membrane grade 3 and 4 mucositis in patients in 1 of 3 groups (salt and soda, continuing GM-CSF, or new GM-CSF). (treatment portion of the study)

Secondary

• Compare the effectiveness of the 2 mouthwashes in preventing RT-induced oral mucositis by the following direct indices:

  • Cumulative RT dose prior to onset of oral mucositis (prevention portion only)
  • Severity of RT-induced oral mucositis at onset and during treatment (using Oral Mucositis Assessment Scale (OMAS))
  • Severity of oral mucositis-related pain at onset and during treatment (using OMAS)
  • Incidence of oral mucositis-related infection at onset and during treatment (using OMAS)
  • Severity of oral mucositis-related problems with ingestion of food and fluids at onset and during treatment (using OMAS)
  • Time to healing of RT-induced oral mucositis.

• Evaluate patients using the following indirect indices of oral mucositis morbidity during the prevention and treatment portions of the study.

  • Tolerance to RT regimen
  • Functional status
  • Quality of life.

OUTLINE: This is a multicenter, randomized, controlled, double-blinded study. Patients are stratified according to radiotherapy dose schedule (standard vs hyperfractionation vs intensity modulation) and concurrent chemotherapy (yes vs no).

• Prevention (no mucositis): Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral sargramostim (GM-CSF) mouthwash, holding it in their mouths and swallowing it in intervals over 1 hour once daily.
  • Arm II: Patients receive oral salt and soda mouthwash, holding it and swallowing it in intervals over 1 hour once daily.

Treatment in both arms continues during 6-7 weeks of radiotherapy and/or the onset of mucositis. Patients also perform PRO-SELF: Mouth Aware (PSMA) twice daily.

• Treatment (onset of mucositis): Patients who are currently using GM-CSF mouthwash continue use as in prevention. Patients who are currently using salt and soda mouthwash are randomized to 1 of 2 treatment arms.

  • Arm III: Patients receive GM-CSF mouthwash as in arm I.
  • Arm IV: Patients receive salt and soda mouthwash as in arm II. In both arms, treatment continues until the mucositis heals. Patients perform PSMA four times daily during and for 3 months after radiotherapy.

Quality of life is assessed at baseline and periodically after radiotherapy.

After completion of study treatment, patients are followed every once a month for 3 months.

Inclusion Criteria

• Histopathologically confirmed diagnosis of head and neck cancer
• Scheduled to undergo continuous course of conventional or hyperfractionated radiotherapy or intensity-modulated radiotherapy (IMRT) with or without concurrent chemotherapy
• Planning to receive a total radiation dose ≥ 5,500 centigray (cGy), administered in a single daily fraction of 180-220 cGy (5 days a week) or twice daily fractions of 110-150 cGy
• Normal baseline oral examinations (no pre-existing lesion)
• Karnofsky performance status 60-100%
• Mentally capable of participating in research protocol
• Expected survival > 4.5 months
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Creatinine ≤ 2.0 mg/dL
• Bilirubin ≤ 2.0 mg/dL
• Aspartate aminotransferase (AST) < 5 times upper limit of normal
• HIV negative

Exclusion Criteria

• No unresolved adverse event from previous therapy

• No prior radiotherapy to the head and neck

• No prior or concurrent brachytherapy

• No prior participation in this study

• No T1 or T2 glottic tumors

• No other serious concurrent medical illness

• No history of insulin-dependent diabetes mellitus

• No prior hypersensitivity reaction to yeast material

• No recent history of oral ulceration, herpes simplex, oral candidiasis, severe gingivitis, active or chronic mucositis, or xerostomia

• No current New York Heart Association class II-IV congestive heart failure

• Not pregnant or nursing

• No chemotherapy, radiotherapy, or other investigational drugs within the past 4 weeks

• No major surgery within the past 2 weeks

• No systemic sargramostim (GM-CSF) within the past 7 days

• No systemic filgrastim (G-CSF) within the past 24 hours

• No systemic long-acting pegfilgrastim within the past 14 days

• No antibiotics, antifungals, or antivirals for oral conditions at baseline

• No other concurrent chemotherapy agent

• No concurrent enrollment on other head and neck studies

• No other concurrent investigational drugs

• No concurrent administration of any of the following:

  • "Magic or miracle mouthwash" containing a palliative mixture of topical anesthetics/analgesics, coating agents, and other medications without an approved indication for topical oral use except liquid antacid formulations (e.g., Maalox® or Mylanta® or their generic equivalents)
  • Other concurrent over-the-counter or prescription mouthwashes beyond the systematic oral care protocol provided by the study or any other drugs or agents to aid in oral hygiene (e.g., chlorhexidine, gluconate, pilocarpine, amifostine, sucralfate tablets or slurry, or benzydamine)
  • Use of corticosteroids for chronic conditions OR within the past 7 days