Efficacy of Prophylactic Treatment With Antibiotics During Concomitant Chemoradiotherapy in Patients With Head and Neck Cancer to Prevent Aspiration Pneumonia

Study Overview
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Brief Summary
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Patients with locally advanced head and neck cancer treated with chemo-radiotherapy have (during and shortly after this treatment) a high risk of developing pneumonia by aspiration. This pneumonia is often associated with a hospital admission and affects the quality of life. The purpose of the study, is to determine whether prophylactic antibiotics may decrease the development of pneumonia. Prophylactic antibiotics means that there are no signs of pneumonia are already

Detailed Description
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Concomitant chemoradiotherapy (CRT) is used in locally advanced head and neck cancer (LAHNC). It will be administered to patients for unresectable disease or for organ preservation as primary treatment. Furthermore, it can be used as postoperative treatment in case high risk recurrent disease is present. This treatment induces a high rate of acute toxicity, such as mucositis, dermatitis, dysphagia, anorexia, and pain. Swallowing dysfunction and aspiration are seen in a high proportion (30%-100%) of patients and with an immense impact on Quality of life (QoL). Around half of the patients will develop an aspiration pneumonia during or shortly after the treatment. Patients, who develop fever during concomitant chemoradiotherapy, are most of the time admitted in the hospital. In the differential diagnosis pneumonia is on the first place in all those patients. The standard diagnostic procedures consist of a chest X-ray and culture of the sputum and blood. Pneumonia can lead to mortality in this frail patient group. The treatment of patients treated with chemoradiotherapy who develop fever and have a definite or suspected pneumonia, is administration of antibiotics, most frequently intravenous amoxicillin/clavulanic acid. LAHNC patients who are smoking and/or with malnutrition are at the highest risk of getting a pneumonia during or after radiotherapy. Because smoking is one of the risk factors of developing head and neck cancer chronic obstructive pulmonary disease (COPD) is frequently present in this group. Also, COPD is a known risk factor for developing pneumonias. Aspiration is seen in all primary sites of head and neck cancer, sometimes it is seen more frequently in patients with cancer of the larynx and hypopharynx. No data of prophylactic administration of antibiotics are available in LAHNC patients. However, a Cochrane review was published to assess the effects of prophylactic antibiotic regimens for the prevention of respiratory tract infections(RTIs) and overall mortality in adults receiving intensive care.

Official Title
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Efficacy and Cost Efficacy of Prophylactic Treatment With Antibiotics During Concomitant Chemoradiotherapy in Patients With Locally Advanced Head and Neck Cancer to Prevent Aspiration Pneumonia. A Randomized Phase II-III Study

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: amoxicillin/clavulanic acid suspension


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with LAHNC which will be treated with CRT as discussed by a multidisciplinary team (i.e. a head and neck surgeon, a medical oncologist, and a radiation oncologist). This can be CRT as primary treatment or postoperative CRT. Written informed consent Expected adequacy of follow-up Exclusion Criteria: Patients with pneumonia within the last 14 days before start of CRT Patients with other infections within the last 14 days within the last 14 days before start of CRT Patients with use of maintenance antibiotics Patients with antibiotic treatment within the last 14 days before start of CRT Patients with an allergy on amoxicillin

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: No prophylactic treatment<br>When a lower airway infection is suspected cultures will be taken and a chest radiography will be made; after that the standard care will be given (in most patients admission to hospital and start of intravenous antibiotics). | |
| Experimental: prophylactic treatment<br>Administration of prophylactic amoxicillin/clavulanic acid suspension, 625 mg tid, start day 29 after the start of CRT until 14 days after the end of CRT. If a lower airway infection is suspected cultures will be taken and a chest radiography will be made; after that the standard care will be given (in most patients admission to hospital and start of intravenous antibiotics) | Drug: amoxicillin/clavulanic acid suspension<br>* 625 mg tid, start day 29 after the start of CRT until 14 days after the end of CRT<br>* Other names: The total duration of the use of amoxicillin /clavulanic acid suspension will be between 20 and 27 days.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the number of definite pneumonia and/ or suspected pneumonia | Definite pneumonia: Evidence of pneumonia on chest radiography or 3 or more of the following: Sustained fever (temperature> 100 f [38°C]), Rales or rhonchi on chest auscultation Sputum Gram stain showing substantial leukocytes Sputum culture showing a respiratory pathogen Suspected pneumonia: At least 2 of the 4 following features are present, without evidence of pneumonia on chest radiography: Sustained fever (temperature> 100 f [38°C]) Rales or rhonchi on chest auscultation Sputum Gram stain showing substantial leukocytes Sputum culture showing a respiratory pathogen | from day 1 of 1 CRT until 3,5 mnd after the last CRT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| effects on Quality of Life | to investigate the effects on QoL after prophylactic treatment with antibiotics Patients fill in the following questionnaires: QLQ-C30, EORTC H&N35, PSHHN, EQ-5D and the VAS, SF-36 | Baseline, Day 28 last day of CRT, 3,5 months after CRT | 
| Number and kind of positive blood cultures |  | from day 1 of 1 CRT until 3,5 mnd after the last CRT | 
| number of admissions to hospital |  | from day 1 of 1 CRT until 3,5 mnd after the last CRT | 
| Number of days of admission |  | from day 1 of 1 CRT until 3,5 mnd after the last CRT | 
| Effects on mortality | Mortality due to definite and/or suspected pneumonia | from day 1 of 1 CRT until 3,5 mnd after the last CRT | 
| effects on mucositis: grade and duration | Mucositis grade according to CTCAE v.4.0 and duration | from day 1 of 1 CRT until 3,5 mnd after the last CRT | 
| side effects of amoxicillin/clavulanic acid | side effects of amoxicillin/clavulanic acid | from day 1 of 1 CRT until 3,5 mnd after the last CRT | 
| Effects on numbers and causative agents of infections at other sites | numbers and causative agents of infections at other sites during follow up (3.5 months after the end of CRT) | during follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Locally Advanced Head and Neck Cancer, LAHNC