Phase III Randomized, Placebo Controlled, Trial Of Docetaxel Versus Docetaxel Plus ZD1839 (Iressa, Gefitinib, NSC 715055) In Performance Status 2 Or Previously Treated Patients With Recurrent Or Metastatic Head And Neck Cancer

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed squamous cell carcinoma of the head and
neck

- Metastatic or locally recurrent disease

- No histologic type WHO 2 or 3 nasopharyngeal carcinoma

- Incurable by local therapies

- Meets 1 of the following criteria:

- ECOG 2 AND no prior chemotherapy for metastatic or locally recurrent head and neck
cancer

- ECOG 0-2 AND received prior chemotherapy (i.e., ≥ 1 prior chemotherapy regimen
[without docetaxel]) for metastatic or locally recurrent disease OR received prior
chemotherapy (without docetaxel) as part of a primary curative therapy within the
past 6 months

- Measurable or non-measurable disease

- Disease within a previously irradiated field is considered measurable provided there
is unequivocal disease progression or biopsy-proven residual carcinoma after
radiotherapy

- Persistent disease after radiotherapy must be biopsy-proven ≥ 8 weeks after
completion of radiotherapy

- No tumors that are unequivocally invading major vessels (e.g. carotid artery)

- No tumor-related hemorrhagic events in the past 3 months that require major medical
intervention (e.g., surgery or embolization)

- No known brain metastasis

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- See Disease Characteristics

Life expectancy

- Not specified

Hematopoietic

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 8.0 g/dL

Hepatic

- Alkaline phosphatase AND AST or ALT meeting criteria for 1 of the following:

- Alkaline phosphatase normal AND AST or ALT ≤ 5 times upper limit of normal (ULN)

- Alkaline phosphatase ≤ 2.5 times UNL AND AST or ALT ≤ 1.5 times ULN

- Alkaline phosphatase ≤ 5 times ULN and AST or ALT normal

- Bilirubin normal

- Renal

- Creatinine < 2.0 mg/dL OR

- Creatinine clearance > 60 mL/min

Cardiovascular

- No uncontrolled hypertension

- No unstable angina

- No congestive heart failure

- No serious arrhythmia requiring medication

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 3 months after study
participation

- No hypercalcemia related to head and neck cancer

- No peripheral neuropathy ≥ grade 2

- No hypersensitivity to gefitinib or any of its excipients

- No severe hypersensitivity to docetaxel or other drugs formulated with polysorbate 80

- No unstable systemic disease

- No active infection

- No significant traumatic injury within the past 3 weeks

- 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 co-existing condition that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No prior monoclonal antibody ABX-EBX or monoclonal antibody MDX-447

- No prior cetuximab

- At least 2 weeks since prior biologic/targeted therapy

- No concurrent immunotherapy

- No concurrent colony-stimulating factors (e.g., filgrastim [G-CSF] or sargramostim
[GM-CSF])

Chemotherapy

- See Disease Characteristics

- Prior paclitaxel allowed provided there was no disease progression during treatment

- At least 4 weeks since prior chemotherapy and recovered

- No prior docetaxel

- No other concurrent chemotherapy

Endocrine therapy

- No concurrent antitumor hormonal therapy

- Concurrent contraceptives, replacement steroids, and dexamethasone allowed

Radiotherapy

- See Disease Characteristics

- At least 3 weeks since prior radiotherapy and recovered

- No concurrent radiotherapy

Surgery

- At least 3 weeks since prior major surgery and recovered

Other

- See Disease Characteristics

- No other prior systemic epidermal growth factor receptor inhibitors, including any of
the following:

- Gefitinib

- Erlotinib

- PKI166

- CI-1033

- EKB-569

- No concurrent CYP3A4 inducers, including any of the following:

- Phenytoin

- Carbamazepine

- Rifampin

- Phenobarbital

- Hypericum perforatum (St. John's wort)

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No concurrent proton pump inhibitors or H2 antagonists within 4 hours after gefitinib
administration

- No concurrent therapeutic anticoagulation

- No other concurrent antitumor therapy

- No other concurrent experimental medications