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.(1) This
treatment induces a high rate of acute toxicity, such as mucositis, dermatitis,
dysphagia, anorexia, and pain.(2) Swallowing dysfunction and aspiration are
seen in a high proportion (30%-100%) of patients and with an immense impact on
Quality of life (QoL).(3;4) 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.(5;6) 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.(7) 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 (8), sometimes
it is seen more frequently in patients with cancer of the larynx and
hypopharynx.(9)

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.
There was a significant reduction in both RTIs (number of studies = 16, odds
ratio (OR) 0.28, 95% confidence interval (CI) 0.20 to 0.38) and total mortality
(number of studies = 17, OR 0.75, 95% CI 0.65 to 0.87) in the treated
group.(10)

In this study (PANTAP study) we want to investigate the efficacy and the cost
efficacy of administration of prophylactic antibiotics during CRT in patients
with LAHNC to prevent aspiration pneumonia.

To observe a decrease in number of definite and/or suspected pneumonia after
prophylactic treatment with antibiotics during CRT in patients with LAHNC.
To observe a decrease in the number of admissions in the hospital
To observe a decrease in the number of days of admission in the hospital
To measure Quality of life (QoL)
To investigate the effects on mortality To observe side effects of amoxicillin
clavulanic acid
To observe causative agents, including amoxicillin-clavulanic acid resistant,
of infections at other sites during follow-up (3.5 months after the end of CRT)

A randomized phase II-III, open label study

Prophylactic treatment
Amoxicillin/clavulanic acid suspension
625 mg tid start day 29 until 2 weeks after CRT

All patients will receive treatment conform current standards. Although the
experimental arm will receive amoxicillin/clavulanic acid tid which is supposed
to decrease the number of definite and/ or suspected pneumonia in LAHNC
patients treated with CRT. Amoxicillin/clavulanic acid will probably not lead
to extra toxicity.