insufficient recruitment

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

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