Cetuximab and Combination Chemotherapy in Patients With Stage III-IV Resectable Oropharynx Cancer

Induction Chemotherapy With Cetuximab, Docetaxel, Cisplatin, and Fluorouracil (ETPF) in Patient With Resectable Stage III-IV Squamous Cell Carcinoma of the Oropharynx

RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as docetaxel, cisplatin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) together with cetuximab may kill more tumor cells.

PURPOSE: This phase II clinical trial is studying how well cetuximab given together with combination chemotherapy works in treating patients with stage III or stage IV oropharynx cancer that can be removed by surgery.

OBJECTIVES:

Primary

• To determine the complete clinical response rate at 3 months in patients with stage III or IV nonmetastatic squamous cell carcinoma of the oropharynx treated with cetuximab, docetaxel, cisplatin, and fluorouracil.

Secondary

• To determine the rate of tumor response.
• To determine progression-free and overall survival.
• To determine the rate of complete pathological response.
• To assess the tolerability of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive cetuximab IV over 1-2 hours on days 1, 8, and 15; docetaxel IV over 1 hour and cisplatin IV over 1 hour on day 1; and fluorouracil IV continuously on days 1-5. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed every 2 months for 1 year and every 3 months for 2 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous cell carcinoma of the oropharynx

  • Stage III (T3 or T1-2, N1-2, M0) or nonmetastatic stage IV (T4 or T1-3, N3, M0) disease
  • Resectable disease

• Measurable or evaluable disease

• Tumor tissue available

PATIENT CHARACTERISTICS:

Inclusion criteria:

• WHO performance status 0-1
• ANC ≥ 1,500/mm3
• Platelet count ≥ 100,000/mm3
• Hemoglobin ≥ 9 g/dL
• Creatinine < 1.5 times upper limit of normal (ULN)
• Creatinine clearance ≥ 60 mL/min
• AST and ALT < 5 times ULN
• Bilirubin < 1.5 times ULN
• Not pregnant or nursing
• Fertile patients must use effective contraception
• Affiliated with social security (including CMU)

Exclusion criteria:

• Cardiovascular accident (myocardial infarction, cerebral vascular accident) within the past 6 months
• Serious and/or uncontrolled cardiac or respiratory disease (pulmonary fibrosis, interstitial pneumopathy)
• Other cancer within the past 5 years except for resected skin cancer, localized cutaneous or totally resected melanoma, or resected carcinoma in situ of the cervix
• Auditory condition precluding the use of cisplatin
• Contraindication due to psychological, social, or geographical reasons that may impede proper monitoring of treatment
• Persons under guardianship or trusteeship, or prisoners of law

PRIOR CONCURRENT THERAPY:

• No prior treatment, including chemotherapy or radiotherapy
• No concurrent phenytoin, live attenuated vaccines, or parenteral aminoglycosides