• Dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) as assessed by CTC v. 3.0 [ Designated as safety issue: Yes ]
  

• Molecular targets analysis of epidermal growth factor receptor (EGFR) downstream signaling pathway as assessed by tissue biopsies and serum cytokines at baseline, days 8 and 29, and 12 weeks after completion of study treatment [ Designated as safety issue: No ]
  
• Efficacy as assessed by imagining, histologically, and clinically at 3 months after completion of study treatment and annually for 5 years [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine the dose-limiting toxicity, toxicity profile, and maximum tolerated dose (MTD) of gefitinib and paclitaxel administered with radiotherapy in patients with advanced or recurrent squamous cell carcinoma of the head and neck.

Secondary

• Determine the efficacy of this regimen in patients treated at the MTD.

OUTLINE: This is a pilot, dose-escalation study of gefitinib and paclitaxel.

Patients receive oral gefitinib once daily beginning on day 1 and continuing until completion of radiotherapy. Patients receive paclitaxel IV over 1 hour on days 8, 15, 22, 29, 36, and 43 and undergo radiotherapy once daily on days 8-12, 15-19, 22-26, 29-33, 36-40, 43-47, 50-54, and 57-61. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of gefitinib and paclitaxel until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A cohort of 6 additional patients receive treatment at the MTD.

Patients are followed monthly for 1 year, every 2 months for 1 year, and then every 3 months for 3 years.

PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 2 years.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed squamous cell (epidermoid) carcinoma of the oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, or maxillary sinus

  • Stage III or IV disease

  • Distant metastases allowed provided both of the following are true:

    • Metastases are confined to the head and neck region
    • Metastases are encompassable in a radiotherapy field with curative intent
• Locally recurrent disease after primary surgery allowed

• Meets 1 of the following criteria:

  • Unresectable disease
  • Patient prefers chemoradiotherapy over surgery
• Measurable disease
• No brain metastases and/or carcinomatous meningitis

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• WBC ≥ 3,000/mm^3
• Hemoglobin > 10 g/dL
• Platelet count > 100,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3

Hepatic

• Bilirubin < 2.0 times upper limit of normal (ULN)
• AST/ALT ≤ 2.5 times ULN

Renal

• Creatinine < 1.5 times ULN OR
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Pulmonary

• No clinically active interstitial lung disease

  • Chronic, stable, asymptomatic radiographic changes allowed

Other

• No prior allergic reaction attributed to compounds of similar chemical or biological composition to study drugs or Cremophor^® EL
• No AIDS or primary immunodeficiencies

• No other malignancy within the past 5 years except curatively treated squamous cell or basal cell skin cancer or carcinoma in situ of the cervix

  • Probability of recurrence of the prior malignancy < 5%
• No other concurrent uncontrolled illness
• No ongoing or active serious infection
• No psychiatric illness or situation that would preclude study compliance or giving informed consent
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy for cancer
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior therapeutic radiotherapy to the head and neck region
• No prior radiotherapy for cancer

Surgery

• See Disease Characteristics
• At least 4 weeks since prior major surgery and recovered

Other

• No prior gefitinib or other epidermal growth factor receptor inhibitors
• More than 4 weeks since prior non-approved or investigational agents

• No concurrent administration of any of the following:

  • Phenytoin
  • Carbamazepine
  • Barbiturates
  • Rifampin
  • Hypericum perforatum (St. John's wort)
  • Oxcarbazepine
  • Rifapentine
  • Amifostine
  • Modafinil
  • Other CYP3A4 enzyme inducers
  • Other anticancer agents or investigational drugs
  • Combination antiretroviral therapy for HIV-positive patients