Table 1 Inclusion and Exclusion criteria of the ESCALOX-trial; (*) A tumour is classified as non-resectable if the probability of a complete tumor resection is estimated at a very low level (non-R0). The decision to classify a tumor as non-resectable has to be confirmed by consent of ENT-specialist, oral surgeon, radio-oncologist, radiologist and pathologist. Detailed criteria of irresectability see Adelstein et al. [55]

▪ Signed written informed consent

▪ Age ≥ 18 ≤ 70 years

▪ Independent of gender

▪ Independent of race

▪ ECOG 0 – 2

▪ Tumor of oral cavity, oropharynx or hypopharynx

▪ Histology: squamous cell carcinoma, HPV-negative

▪ Curative treatment intended

▪ Tumor is classified as irresectable [11]*

▪ Woman of child-bearing age: negative pregnancy test in serum

▪ Contraception in male and female patients and their partners if of childbearing potential, willingness to use effective contraceptive method for the study duration and 2 months post therapy

▪ Sufficient bone marrow reserves during 7 days before study inclusion; (leukocytes ≥ 4 × 10⁹/l, absolute no. of neutrophiles (ANC) ≥ 2 × 10⁹/;

▪ thrombocyte count ≥ 100 × 10⁹/l; hemoglobin ≥ 10 g/dl)

▪ adaequate liver function during 7 days before study inclusion (total bilirubine ≤ 2,5 × ULN (upper limit of normal), ASAT/ALAT ≤ 2,5 × ULN,

▪ alkaline phosphatase ≤ 2,5 × ULN of the institution’s normal value)

▪ adequate kidney function during 7 days before study inclusion; serum creatinine ≤ 130 μmol/l; creatinine clearance ≥ 70 ml/min

▪ all patients should have a dental examination before starting therapy and if necessary be treated, adaptation of a teeth protection bar

▪ a percutane feeding tube should be applied before start of treatment

▪ Infiltration of the mandible and/or larynx

▪ HPV-positive proven tumors

▪ impaired renal and/or liver function

▪ secondary malignancy, unknown primary cancer, nasopharynx cancer or

▪ salivary gland cancers

▪ Metastatic disease

▪ Another cancer within 5 years of study entry

▪ Serious concomitant disease or medical condition

▪ Pregnancy or lactation

▪ Women of child-bearing potential with unclear contraception (postmenopausal

▪ women must have been amenorrheal for at least 12 months to be considered of non-childbearing potential)

▪ previous treatment with chemotherapy, radiotherapy or surgery in head and neck (except an excisional biopsy or biopsy for histology and surgery for benign disease)

▪ concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days prior to study screening

▪ life expectancy of < 1 year

▪ contraindications to receive Cisplatin

▪ social situations that limit compliance with study requirements