Inclusion Criteria:

- Newly diagnosed tumors classified as stage III-IV located in the larynx, oropharynx
and hypopharynx (unknown primary should be excluded; oral cavity are not eligible)

- Human papillomavirus(HPV)/p16 negative (≤70% positively stained cells), assessed
locally (please refer to chapter 1.2)

- Histopathological diagnosis of invasive squamous cell carcinoma in the primary tumor

- World Health Organization (WHO) performance 0-2

- All Hematology and biochemical investigations, should be done within 4 weeks before
randomization (maximum 6 weeks before treatment starts)

- Normal bone marrow function based on routine blood samples, i.e. neutrophils ≥ 1.0 x
109/L, platelets ≥ 75 x 109/L, hemoglobin ≥ 10.0 g/dL or 6.2 mmol/L

- Normal kidney function creatinine clearance ≥ 60ml/min, and Electrolyte balance:
calcium ≤ 11.5 mg/dl or 2.9 mmol/l, magnesium ≥ 1.2 mg/dl or 0.5 mmol/l

- Normal liver function assessed by routine laboratory examinations, i.e. bilirubin <
1.5 x Upper Limit of Normal (ULN), Aspartate aminotransferase (AST)< 3 x ULN,
alkaline phosphatases < 3 x ULN

- No prior or current anticancer treatment to the head and neck area (e.g. radical
attempted or tumor reductive surgery, neo-adjuvant chemotherapy, Epidermal Growth
Factor Receptor (EGFR) inhibitors or radiotherapy).

- Patients must be candidate for curative intent external beam chemo-radiotherapy, and
must be expected to complete the treatment.

- All patients should have an oral and dental examination including preferably clinical
and radiological examination. Whenever indicated, extraction of dental elements
should be carried out at least 10 to 14 days before treatment start.

- Radiotherapy planned to start within acceptable delay (preferably within 2 weeks and
a maximum of 4 weeks from randomization).

- Radiotherapy planned to start within 8 weeks from baseline imaging tumor assessment.

- Absence of any psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol and follow-up schedule;
those conditions should be discussed with the patient before randomization in the
trial

- All subjects must agree to abstain from donating blood while receiving therapy and
for four weeks following discontinuation of therapy.

- All subjects must agree not to share study medication with another person and to
return all unused study drug to the investigator.

- Before patient registration, written informed consent must be given according to
International Conference on Harmonisation /Good Clinical Practice (ICH/GCP), and
national/local regulations (including material acquisition for central testing of the
hypoxic signature)

Exclusion Criteria:

- No distant metastasis (M0)

- Patients should not be in a state or condition that could be expected to influence
the outcome of treatment, or complicate the assessment or the treatment follow-up, or
(apart from the present disease) reduce the life expectancy.

- Patients should not have symptoms of peripheral neuropathy, assessed by medical
history.