cetuximab plus radiotherapy versus cisplatin plus radiotherapy in locally advanced head and neck cancer

Conditions: Head and Neck Neoplasms; Laryngeal Neoplasms; Mouth Neoplasms; Pharyngeal Neoplasms

Summary: background: concomitant radiotherapy and cisplatin (cddp) based chemotherapy is the standard treatment for la-nhscc. this combined modality treatment is linked with considerable acute local and systemic toxicity.egfr is overexpressed in 90-100% of the hnscc cases and is considered an unfavourable prognostic marker. egfr costitutive activation is linked with hnscc pathogenesis. cetuximab is a monoclonal anti-egfr antibody blocking the activation of the receptor and signal transduction. cetuximab combined with radiotherapy is superior to radiotherapy only in the treatment of la-hnscc and is characterized by an acceptable toxicity profile. rationale: a direct comparison between concomitant chemoradiotherapy with cisplatin and the concomitant treatment with radiotherapy associated to cetuximab does not exist. study design: arm a: radical radiotherapy (doses and volumes) concomitant with chemotherapy with cisplatin (40 mg/mq/week) arm b: radical radiotherapy (doses and volumes) concomitant with therapy with the monoclonal antibody cetuximab (400 mg/m2 \["loading dose"\] and subsequently 250 mg /m2/week)

primary objectives: evaluation and comparison of the compliance of the two treatments; secondary objectives: evaluation and comparison of the grade and incidence of acute toxicity; evaluation and comparison of local control; evaluation and comparison of event free survival (both local control and distant metastases); evaluation and comparison of cause specific and overall survival. inclusion/exclusion criteria * histologically confirmed squamous cell carcinoma (biopsy obtained from the tumor and/or from its lymphnodal metastases) originating from oral cavity, oropharynx, hypopharinx, supraglottic larynx; * locally advanced disease, defined by one of the following criteria: every t, n+, m0 ( t1, n1 cases excluded); t3-4, n0, m0; * not a nasopharynx, paranasal sinuses, salivary glands tumor; * general conditions and concomitant diseases not considered a contraindication for chemotherapy or curative radiotherapy; * no other surgical, chemotherapeutic or radiotherapic treatments for ent region tumors or for tumors of other anatomical sites (with the exception of non-melanoma cutaneous tumors and of the carcinoma in situ of the uterine cervix and of other solid tumors whose primary treatment has been completed more than 3 years before the accrual in this study and never relapsed since primary treatment (the patient having been since then continuously disease- free); * availability for follow-up; * signed informed consent; * an interval of maximum 3 weeks between staging procedures for local disease and randomization * an interval of maximum 2 weeks between randomization and the onset of the treatment

Eligibility criteria:
inclusion criteria: * histologically confirmed squamous cell carcinoma (with biopsy on the primary and / or lymph node metastases) of the oral cavity, oropharynx, hypopharynx, larynx supraglottix; * locally advanced disease, defined by one of the following criteria: any t, n +, m0 (excluding t1, n1), t3-4, n0, m0; * not cancer nasopharynx or paranasal sinuses or salivary glands; * general conditions and associated diseases which does not allow to perform chemotherapy or radiotherapy in a radical view; * no other surgical treatments, chemotherapy or radiotherapy for cancer of head and neck or elsewhere, except non-melanoma skin cancer or in situ cervical cancer and other solid tumors for which radical treatment has been completed \> three years prior to enrollment in the study and for which the patient has remained continuously free of disease; * accessibility to follow-up; * signing of informed consent; * interval between examinations of local staging and randomization, maximum 3 weeks * interval between randomization and initiation of treatment, maximum 2 weeks exclusion criteria: * age \<18 years * ecog performance status \> 0-1 * hemoglobin \<9 g / dl * counts of granulocytes, total \<1.5 x 10 \^ 9 / l * platelet count \<100 x 10 \^ 9 / l * bilirubin\> 1.5 times upper limit of normal (uln) * ast or alt\> 3 times uln * creatinine clearance \> 50 ml/min * mg \> 0.5 mmol/l * pregnancy or lactation * presence of allergy to study drug or to the excipients used in their formulation * peripheral neuropathy ≥ grade 2 (ctcae v3.0) * hearing loss / tinnitus ≥ grade 3 (ctcae v3.0) * one of the following conditions: * myocardial infarction within 12 months prior to randomization * severe congestive heart failure * unstable angina * cardiomyopathy in act * ventricular arrhythmia * uncontrolled hypertension * severe psychotic disorders in act * severe infection in act * any other serious illness that could interfere with the administration of the therapy provided by the protocol

Keywords: head and neck cancer radiotherapy cetuximab cisplatin