Dysphagia, Head and Neck Cancer, Mucositis, Xerostomia
Conditions
Keywords
xerostomia, mucositis, dysphagia, radiation toxicity, chemotherapeutic agent toxicity, stage III squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the hypopharynx, recurrent squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the larynx, stage III verrucous carcinoma of the larynx, stage IV squamous cell carcinoma of the larynx, stage IV verrucous carcinoma of the larynx, recurrent squamous cell carcinoma of the larynx, recurrent verrucous carcinoma of the larynx, stage III squamous cell carcinoma of the lip and oral cavity, stage III verrucous carcinoma of the oral cavity, stage IV squamous cell carcinoma of the lip and oral cavity, stage IV verrucous carcinoma of the oral cavity, recurrent squamous cell carcinoma of the lip and oral cavity, recurrent verrucous carcinoma of the oral cavity, stage III squamous cell carcinoma of the nasopharynx, stage IV squamous cell carcinoma of the nasopharynx, recurrent squamous cell carcinoma of the nasopharynx, stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx, recurrent squamous cell carcinoma of the oropharynx, salivary gland squamous cell carcinoma, stage III salivary gland cancer, stage IV salivary gland cancer, recurrent salivary gland cancer
Brief summary
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Amifostine may decrease the side effects caused by chemotherapy and radiation therapy. It is not yet known whether chemotherapy and radiation therapy are more effective with or without amifostine in treating head and neck cancer. PURPOSE: This randomized phase II trial is studying amifostine to see how well it works compared with standard care in reducing side effects in patients undergoing chemotherapy and radiation therapy for stage III or stage IV head and neck cancer.
Detailed description
OBJECTIVES: Primary * To compare the incidence and severity of acute and chronic swallowing dysfunction in stage III or IV head and neck cancer patients receiving concurrent chemoradiation with or without amifostine Secondary * To assess the relative incidence and severity of acute and chronic xerostomia in stage III or IV head and neck cancer patients receiving chemoradiation with or without amifostine. * To assess the relative incidence and severity of mucositis and mucositis-related inflammation in stage III or IV head and neck cancer patients receiving chemoradiation with or without amifostine. * To assess the effects of dysphagia, xerostomia, and mucositis-related inflammation on nutritional, physical, and functional status OUTLINE: Patients undergo intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy comprising carboplatin and paclitaxel weekly. Patients are randomized to 1 of 2 treatment arms. * Arm I (standard of care): Patients are further divided into 1A or 1B. * Arm IA: Standard of care plus standardized nutrition therapy (SNT) * Arm IB: Standard of care plus standardized nutrition therapy plus low weight resistance training (LWRT). * Arm II (amifostine): Patients are further divided into 2A or 2B. * Arm IIA: Amifostine 500mg diluted in 2.9 ml injected 30-60 minutes prior to each radiation dose plus standardized nutrition therapy * Arm IIB: Amifostine 500mg diluted in 2.9 ml injected 30-60 minutes prior to each radiation dose plus standardized nutrition therapy plus low weight resistance training In all arms, patients undergo swallowing function, dietary, body composition, muscle, and physical and functional performance measurements at baseline and at 1, 3, and 6 months post-therapy. Quality of life, salivary production, fatigue, and symptoms (including swallowing/eating foods, appetite, weight loss/nutrition, pain, and speech/communication) are assessed at baseline and at 1, 3, and 6 months post-therapy. Anthropometric measurements are also performed at the above time points and at mid-therapy. Blood samples and buccal rinses are collected at baseline and at 1, 3, and 6 months post-therapy for biomarker studies and for proteomic and genomic analysis by liquid chromatography and tandem mass spectrometry. After completion of study treatment, patients are followed at 1, 3, and 6 months.
Interventions
BEHAVIORALexercise intervention
Patients undergo low weight resistance training.
DRUGamifostine trihydrate
Given subcutaneously
PROCEDUREtherapeutic dietary intervention
Patients undergo specialized nutrition therapy (SNT) including dietitian counseling and calorie goal instruction.
Sponsors
National Cancer Institute (NCI)
Vanderbilt-Ingram Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age greater than 21 * Biopsy proven stage 3 or 4 squamous cell carcinoma of the larynx, pharynx, oral cavity or salivary glands * No prior history of active cancer within three years other than non-melanoma skin cancer, early stage prostate or early stage cervical cancer * controlled co-morbid disease * ECOG PS of 0-3 * Plan for definitive or post-operative CCR within 4 weeks * Written informed consent * Working telephone * May have received prior induction chemotherapy * Agree to use only study supplied liquid nutrition supplements or dietary supplements, for per os or feeding tube intake
Exclusion criteria
* Diagnosed HIV or AIDS * History of ETOH or drug abuse within 3 months * Pregnant or lactating * On steroid medication or prescribed NSAIDs * Consuming specialty nutrition supplements containing additional amounts of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) * On orexigenic (appetite stimulant) medication. * Uncontrolled comorbid disease defined as: a) severe cardiac disease Class III or greater; b) blood pressure \> 160/95; c) uncontrolled pain * Does not have working telephone.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Each Degree of Swallowing Dysfunction | 6 months after concurrent chemotherapy and radiation | Grade of swallowing dysfunction as measured by the modified barium swallow score: grade 1, normal; grade 2, within functional limits; grade 3, mild impairment; grade 4, mild to moderate impairment; grade 5, moderate impairment; grade 6, moderate to severe impairment; grade 7, severe impairment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stimulated and Unstimulated Salivary Production | 6 months after concurrent chemotherapy and radiation | Unstimulated and stimulated salivary production, measured in mL/minute. Unstimulated salivary production is determined by expectoration of passively accumulated secretions accumulated in three 2-minute periods. Stimulated salivary production is determined by chewing paraffin wax with expectoration of passively accumulated secretions accumulated in three 2-minute periods. |
| Number of Patients With Oral Mucositis by Grade | 6 months after concurrent chemotherapy and radiation | Measured by Common Toxicity Criteria (CTC) v. 3.00 = no mucositis (minimum score), 1 = mild mucositis, 2 = moderate mucositis, 3 = severe mucositis, 4 = life-threatening, disabling mucositis, 5 = death (worst score). |
| Changes in the Amount and Texture of Food Consumed | at baseline, at 1 month, 3 months and 6 months post-chemoradiation | Patients are asked to note their food intake in terms of amount and texture over the past 24 hours as measured by 24-hour dietary recalls. |
| Changes in the Frequency and Types of Dietary Intakes | at baseline, at 1 month, 3 months and 6 months post-chemoradiation | Patients are asked to note their food intake in terms of amount and texture over the past 24 hours as measured by 24 hour dietary recalls. |
Countries
United States
Participant flow
Recruitment details
This study was open to accrual from 01/01/2006 through 03/05/2008.
Pre-assignment details
43 patients consented, one was ineligible for a total of 42 patients on study.
Participants by arm
| Arm | Count |
|---|---|
| Arm IA Patients undergo specialized nutrition therapy (SNT) including dietitian counseling and calorie goal instruction. | 8 |
| Arm IB Patients undergo SNT and low weight resistance training (LWRT). | 12 |
| Arm IIA Patients receive amifostine subcutaneously (SC) 30-60 minutes prior to each dose of intensity-modulated radiotherapy (IMRT). Patients also undergo SNT as in arm IA. | 12 |
| Arm IIB Patients receive amifostine SC 30-60 minutes prior to each dose of IMRT. Patients also undergo SNT and LWRT as in arm IB. | 10 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Physician Decision | 0 | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Arm IB | Arm IIA | Arm IA | Arm IIB | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 10 Participants | 8 Participants | 10 Participants | 40 Participants |
| Age, Continuous | 55 years STANDARD_DEVIATION 1 | 54 years STANDARD_DEVIATION 1 | 51 years STANDARD_DEVIATION 1 | 55 years STANDARD_DEVIATION 1 | 54 years STANDARD_DEVIATION 1 |
| Region of Enrollment United States | 12 participants | 12 participants | 8 participants | 10 participants | 42 participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 3 Participants | 0 Participants | 6 Participants |
| Sex: Female, Male Male | 11 Participants | 10 Participants | 5 Participants | 10 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 8 | 12 / 12 | 10 / 12 | 8 / 9 |
| serious Total, serious adverse events | 0 / 8 | 0 / 12 | 2 / 12 | 4 / 9 |
Outcome results
Primary
Number of Patients With Each Degree of Swallowing Dysfunction
Grade of swallowing dysfunction as measured by the modified barium swallow score: grade 1, normal; grade 2, within functional limits; grade 3, mild impairment; grade 4, mild to moderate impairment; grade 5, moderate impairment; grade 6, moderate to severe impairment; grade 7, severe impairment
Time frame: 6 months after concurrent chemotherapy and radiation
Population: One patient (Arm 2B) did not undergo the 6-month study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm IA | Number of Patients With Each Degree of Swallowing Dysfunction | No. of patients with dysphagia grade 0 | 2 participants |
| Arm IA | Number of Patients With Each Degree of Swallowing Dysfunction | No. of patients with dysphagia grade 1 | 1 participants |
| Arm IA | Number of Patients With Each Degree of Swallowing Dysfunction | No. of patients with dysphagia grade 2 | 1 participants |
| Arm IA | Number of Patients With Each Degree of Swallowing Dysfunction | No. of patients with dysphagia grade 3 | 3 participants |
| Arm IA | Number of Patients With Each Degree of Swallowing Dysfunction | No. of patients with dysphagia grade 4 | 0 participants |
| Arm IA | Number of Patients With Each Degree of Swallowing Dysfunction | Not Accessible | 1 participants |
| Arm IB | Number of Patients With Each Degree of Swallowing Dysfunction | Not Accessible | 4 participants |
| Arm IB | Number of Patients With Each Degree of Swallowing Dysfunction | No. of patients with dysphagia grade 3 | 1 participants |
| Arm IB | Number of Patients With Each Degree of Swallowing Dysfunction | No. of patients with dysphagia grade 0 | 1 participants |
| Arm IB | Number of Patients With Each Degree of Swallowing Dysfunction | No. of patients with dysphagia grade 2 | 1 participants |
| Arm IB | Number of Patients With Each Degree of Swallowing Dysfunction | No. of patients with dysphagia grade 1 | 5 participants |
| Arm IB | Number of Patients With Each Degree of Swallowing Dysfunction | No. of patients with dysphagia grade 4 | 0 participants |
| Arm IIA | Number of Patients With Each Degree of Swallowing Dysfunction | No. of patients with dysphagia grade 1 | 4 participants |
| Arm IIA | Number of Patients With Each Degree of Swallowing Dysfunction | No. of patients with dysphagia grade 2 | 2 participants |
| Arm IIA | Number of Patients With Each Degree of Swallowing Dysfunction | No. of patients with dysphagia grade 3 | 1 participants |
| Arm IIA | Number of Patients With Each Degree of Swallowing Dysfunction | Not Accessible | 3 participants |
| Arm IIA | Number of Patients With Each Degree of Swallowing Dysfunction | No. of patients with dysphagia grade 4 | 0 participants |
| Arm IIA | Number of Patients With Each Degree of Swallowing Dysfunction | No. of patients with dysphagia grade 0 | 2 participants |
| Arm IIB | Number of Patients With Each Degree of Swallowing Dysfunction | No. of patients with dysphagia grade 4 | 0 participants |
| Arm IIB | Number of Patients With Each Degree of Swallowing Dysfunction | Not Accessible | 1 participants |
| Arm IIB | Number of Patients With Each Degree of Swallowing Dysfunction | No. of patients with dysphagia grade 1 | 4 participants |
| Arm IIB | Number of Patients With Each Degree of Swallowing Dysfunction | No. of patients with dysphagia grade 3 | 0 participants |
| Arm IIB | Number of Patients With Each Degree of Swallowing Dysfunction | No. of patients with dysphagia grade 0 | 3 participants |
| Arm IIB | Number of Patients With Each Degree of Swallowing Dysfunction | No. of patients with dysphagia grade 2 | 1 participants |
Secondary
Changes in the Amount and Texture of Food Consumed
Patients are asked to note their food intake in terms of amount and texture over the past 24 hours as measured by 24-hour dietary recalls.
Time frame: at baseline, at 1 month, 3 months and 6 months post-chemoradiation
Population: Due to loss of funding, sufficient data for analysis was not collected.
Secondary
Changes in the Frequency and Types of Dietary Intakes
Patients are asked to note their food intake in terms of amount and texture over the past 24 hours as measured by 24 hour dietary recalls.
Time frame: at baseline, at 1 month, 3 months and 6 months post-chemoradiation
Population: Due to loss of funding, sufficient data for analysis was not collected.
Secondary
Number of Patients With Oral Mucositis by Grade
Measured by Common Toxicity Criteria (CTC) v. 3.00 = no mucositis (minimum score), 1 = mild mucositis, 2 = moderate mucositis, 3 = severe mucositis, 4 = life-threatening, disabling mucositis, 5 = death (worst score).
Time frame: 6 months after concurrent chemotherapy and radiation
Population: Participants available for 6-month follow-up oral examination. No 6-month follow-up data were available for the following numbers of patients: Arm 1A (1), Arm 1B (4), Arm 2A (3), Arm 2B (2).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm IA | Number of Patients With Oral Mucositis by Grade | No. of patients with grade 4, disabling mucositis | 0 participants |
| Arm IA | Number of Patients With Oral Mucositis by Grade | No of patients with grade 3, severe mucositis | 3 participants |
| Arm IA | Number of Patients With Oral Mucositis by Grade | No. of patients with grade 1, mild mucositis | 0 participants |
| Arm IA | Number of Patients With Oral Mucositis by Grade | No. of patients with grade 0, no mucositis | 3 participants |
| Arm IA | Number of Patients With Oral Mucositis by Grade | No. of patients with grade 5 mucositis, death | 0 participants |
| Arm IA | Number of Patients With Oral Mucositis by Grade | No of patients with grade 2, moderate mucositis | 1 participants |
| Arm IB | Number of Patients With Oral Mucositis by Grade | No of patients with grade 2, moderate mucositis | 0 participants |
| Arm IB | Number of Patients With Oral Mucositis by Grade | No of patients with grade 3, severe mucositis | 0 participants |
| Arm IB | Number of Patients With Oral Mucositis by Grade | No. of patients with grade 1, mild mucositis | 4 participants |
| Arm IB | Number of Patients With Oral Mucositis by Grade | No. of patients with grade 0, no mucositis | 4 participants |
| Arm IB | Number of Patients With Oral Mucositis by Grade | No. of patients with grade 4, disabling mucositis | 0 participants |
| Arm IB | Number of Patients With Oral Mucositis by Grade | No. of patients with grade 5 mucositis, death | 0 participants |
| Arm IIA | Number of Patients With Oral Mucositis by Grade | No of patients with grade 2, moderate mucositis | 1 participants |
| Arm IIA | Number of Patients With Oral Mucositis by Grade | No. of patients with grade 0, no mucositis | 6 participants |
| Arm IIA | Number of Patients With Oral Mucositis by Grade | No. of patients with grade 1, mild mucositis | 2 participants |
| Arm IIA | Number of Patients With Oral Mucositis by Grade | No of patients with grade 3, severe mucositis | 0 participants |
| Arm IIA | Number of Patients With Oral Mucositis by Grade | No. of patients with grade 4, disabling mucositis | 0 participants |
| Arm IIA | Number of Patients With Oral Mucositis by Grade | No. of patients with grade 5 mucositis, death | 0 participants |
| Arm IIB | Number of Patients With Oral Mucositis by Grade | No. of patients with grade 5 mucositis, death | 0 participants |
| Arm IIB | Number of Patients With Oral Mucositis by Grade | No. of patients with grade 4, disabling mucositis | 0 participants |
| Arm IIB | Number of Patients With Oral Mucositis by Grade | No. of patients with grade 1, mild mucositis | 3 participants |
| Arm IIB | Number of Patients With Oral Mucositis by Grade | No of patients with grade 2, moderate mucositis | 2 participants |
| Arm IIB | Number of Patients With Oral Mucositis by Grade | No. of patients with grade 0, no mucositis | 3 participants |
| Arm IIB | Number of Patients With Oral Mucositis by Grade | No of patients with grade 3, severe mucositis | 0 participants |
Secondary
Stimulated and Unstimulated Salivary Production
Unstimulated and stimulated salivary production, measured in mL/minute. Unstimulated salivary production is determined by expectoration of passively accumulated secretions accumulated in three 2-minute periods. Stimulated salivary production is determined by chewing paraffin wax with expectoration of passively accumulated secretions accumulated in three 2-minute periods.
Time frame: 6 months after concurrent chemotherapy and radiation
Population: Patients who underwent salivary testing at 6 months. The following patients were not available at 6- months for testing for salivary production: Arm 1A (1), Arm 1B (4), Arm 2A (3), Arm 2B (2)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm IA | Stimulated and Unstimulated Salivary Production | Unstimulated | 0.64 mL per minute | Standard Deviation 0.37 |
| Arm IA | Stimulated and Unstimulated Salivary Production | Stimulated | 0.72 mL per minute | Standard Deviation 1.85 |
| Arm IB | Stimulated and Unstimulated Salivary Production | Stimulated | 5.04 mL per minute | Standard Deviation 3.16 |
| Arm IB | Stimulated and Unstimulated Salivary Production | Unstimulated | 1.70 mL per minute | Standard Deviation 1.44 |
| Arm IIA | Stimulated and Unstimulated Salivary Production | Unstimulated | 1.38 mL per minute | Standard Deviation 1.9 |
| Arm IIA | Stimulated and Unstimulated Salivary Production | Stimulated | 5.25 mL per minute | Standard Deviation 3.39 |
| Arm IIB | Stimulated and Unstimulated Salivary Production | Unstimulated | 0.68 mL per minute | Standard Deviation 0.32 |
| Arm IIB | Stimulated and Unstimulated Salivary Production | Stimulated | 0.94 mL per minute | Standard Deviation 2.25 |