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
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
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
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
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
C. van Herpen, MD
University Medical Centre Nijmegen
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)