The Effects of Whole-Food Intervention on Mucositis in Patients Being Treated for Head and Neck Cancer with Radiation with or Without Chemotherapy
The American Cancer Society estimates more than 30,000 new cases of oral and throat cancer occur annually in the United States. Treatment of cancer is increasingly effective but associated with short- and long-term side effects. Oral side effects, including oral mucositis (inflammation of the lining of the mouth ranging from redness to ulceration), remain a major source of illness despite the use of a variety of agents to treat them. Mucositis is a common side effect suffered by about 80% or more of patients treated with radiation and chemotherapy for head and neck cancers and typically becoming symptomatic in the second or third week of therapy.
The present study is a two-center, open-label, pilot study to evaluate the efficacy, safety, tolerability and compliance of a whole-food intervention with standard of care for head and neck cancer patients (excluding early stage glottic malignancies) at risk of developing radiation-therapy-induced oral and oropharyngeal mucositis, with or without chemotherapy. This is a pilot study to determine feasibility for future studies and is not intended to show statistical significance. The primary objectives are to determine whether patients will use a whole food intervention 4-6 times daily to prevent and treat mucositis.
Study Design
This is a 10-week study. The primary endpoints of efficacy, safety, tolerability and compliance will be analyzed throughout the duration of the study. The initial dose whole-food intervention will be administered at the start of radiation therapy with or without chemotherapy. Subjects will be given the whole-food intervention plus standard of care. Standard of care may include various mouthwashes routinely prescribed by the treating oncology physician.
Chart review and patient questionnaires will be used to establish whether a treatment break or dose reduction for radiation or chemotherapy was required due to mucositis-related symptoms. Mucositis-related pain and inhibition of oral intake will be quantified by using validated assessment tools. Weight loss or gain, diarrhea, constipation or no change in bowel function and the use of conventional medications for mucositis will be recorded. Complete nutritional chemistry profiles and CBCs will be taken at the beginning and end of the study. The patient will continue to use standard mucositis therapies, if desired, as prescribed by the treating oncology physician.
The whole-food intervention consists of yogurt, butter, honey, vanilla and glutamine, with approximately 2 TBSP of the mixture taken 4 to 6 times daily. The ingredients used in the whole-food intervention have individually been studied and their potential benefit for radiation- and/or chemotherapy-related mucositis is reviewed below.
Honey
Forty patients (40) with head and neck cancer requiring radiation therapy were randomized to either usual care or 20ml honey before, immediately after, and 6 hours after each radiation therapy. The honey group had significant reductions in symptomatic high-grade mucositis (20 vs. 50%). 55% of treated patients maintained or gained weight, compared to 25% in controls (p=0.053). None of the treated group required interruption in treatment, compared to 20% of controls (p=0.0373).
Glutamine
Seventeen (17) patients with head and neck cancer requiring radiation therapy were randomized to either normal saline rinses or a solution of 16g glutamine in 240ml saline, with 30ml swished for 3 minutes, then expectorated, 4 times daily throughout the course of radiation therapy treatment. There was a reduction in the duration of high-grade subjective mucositis (p=0.038). No effect on body weight or interruption of therapy was seen.
One hundred ten (110) children undergoing chemotherapy and hematopoietic stem cell transplant (HSCT) were randomized to either glutamine up to 4g daily or glycine controls. The glutamine group had significantly less intravenous narcotic use (p=0.03) and need for TPN (p=0.01), with a non-significant trend towards a lower mean mucositis score.
Probiotics
Probiotics have not been studied specifically in mucositis. However, overgrowth of bacteria has been associated with radiation-induced mucositis and topical antimicrobials have been associated with a reduction in mucositis severity and duration. Probiotics have been shown to be beneficial in other gastrointestinal overgrowth syndromes including pouchitis and Clostridium difficile diarrhea; and have demonstrated anti-inflammatory properties in ulcerative colitis. It is speculated that the addition of a mixture of probiotics from a traditional food, lactobacilli found in yogurt, would be beneficial. Lactobacilli can, on rare occasions, cause bacteremia, and it would be reasonable to avoid their use in neutropenic patients. However it is equally notable and reassuring that probiotic therapy was without any adverse effects in a recent study of neutropenic patients.
Given the negative impact on clinical outcomes and quality-of-life associated with mucositis, this study aims to provide in one product four foods that individually have promise for benefit in the treatment of mucositis associated with radiation therapy and chemotherapy. This product is inexpensive, simple to produce in any kitchen and provides useful nutrition at the same time as potentially being a useful treatment to prevent or ameliorate mucositis. This whole-food intervention is not expected to interfere with any of the other therapies currently being used for mucositis. This study will involve giving the patient the whole-food intervention with instructions to take 3 portioning cups per day to be taken gradually throughout the day, from the beginning of therapy and for 4 weeks after therapy. Typically this will mean the whole-food intervention will be used for a total of about 10 weeks.
Subjects eligible to participate in this clinical trial must meet all of the following criteria.
Inclusion Criteria
Ages eligible for study: 18 years and above; genders eligible for study: both
- Histopathologically confirmed diagnosis of head and neck cancer
- Scheduled to undergo continuous course of radiation therapy with or without chemotherapy.
- No other serious concurrent medical illness as determined by Investigator.
- Absolute neutrophil count ≥ 500/mm3
- Platelet count ≥50,000/mm3
- No history of insulin-dependent diabetes mellitus
- No prior hypersensitivity reaction to compound components
Exclusion Criteria
- Dislike of the available forms of the Whole-Food Intervention
- Allergy or food intolerance relevant to the ingredients
- Lack of access to refrigerated storage for the nutritional therapy
- Inability or unwillingness to participate twice a week
- Inability to swallow
- Being treated for HIV with HIV medications
Experience to Date
Two participants were enrolled in the pilot study phase and have completed study treatment. Both men were 100% compliant in taking the whole-food intervention as prescribed. They both developed mucositis that was rated as minor oral sores. They were able to continue eating solid food, and the oral sores resolved within a couple days. They did not have to interrupt their radiation treatment. One man also received chemotherapy. There were no reported adverse events.
The patients’ assessment of oral symptoms was graded on a scale of 0 to 21. The highest score reported was 9. The physician assessment of toxicity grading of mucositis was graded on a Grade 0 (none), Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (life threatening). Grade 1 was not reported until week 5 of the radiation therapy. There was a brief period of Grade 2 being reported which quickly resolved to Grade 1 with increased doses of the whole-food intervention.
If you are interested in learning more about the study or would like to refer a patient, please contact Miles Hassell, M.D., at 503-291-1777 or Chris Bielke, R.N., at 503-216-0246. www.providence.org/integrativemedicine