A Pilot Phase I Dose Escalation Study Of The EGFR Tyrosine Kinase Inhibitor Gefitinib (Iressa) Combined With Paclitaxel (Taxol) And External Beam Radiation Therapy In Patients With Advanced Squamous Cell Carcinoma Of The Head And Neck (SCCHN)
A Pilot Phase I Dose Escalation Study Of The EGFR Tyrosine Kinase Inhibitor Gefitinib (Iressa) Combined With Paclitaxel (Taxol) And External Beam Radiation Therapy In Patients With Advanced Squamous Cell Carcinoma Of The Head And Neck (SCCHN)
RATIONALE: Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving gefitinib and paclitaxel together with radiation therapy may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of gefitinib and paclitaxel when given together with radiation therapy in treating patients with advanced or recurrent squamous cell carcinoma (cancer) of the head and neck.
OBJECTIVES:
Primary
Secondary
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:
Locally recurrent disease after primary surgery allowed
Meets 1 of the following criteria:
Measurable disease
No brain metastases and/or carcinomatous meningitis
PATIENT CHARACTERISTICS:
Age
Performance status
Life expectancy
Hematopoietic
Hepatic
Renal
Cardiovascular
Pulmonary
No clinically active interstitial lung disease
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
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
Chemotherapy
Endocrine therapy
Radiotherapy
Surgery
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: