Gefitinib and Etoposide in Treating Patients With Advanced Prostate Cancer That Did Not Respond to Hormone Therapy

OBJECTIVES:

Primary

- Determine the activity of gefitinib and etoposide, in terms of overall response rate, in
patients with hormone-refractory advanced prostate cancer previously treated with
docetaxel-based therapy.

Secondary

- Determine the toxicity of this regimen in these patients.

- Determine whether related biomarkers can help predict response in patients treated with
this regimen.

OUTLINE: This is a nonrandomized study.

Patients receive oral gefitinib once daily on days 1-28 and oral etoposide once daily on days
1-14. Treatment repeats every 28 days in the absence of disease progression or unacceptable
toxicity.

Patients undergo blood sample collection at baseline and periodically during study for
correlative studies. Blood samples are analyzed by enzyme-linked immunosorbent assays for
biomarkers (e.g., VEGF, basic fibroblast growth factor, and anti-EGFR antibody titers) in
order to determine whether one or more of these biomarkers can predict response.

After completion of study therapy, patients are followed periodically.

DISEASE CHARACTERISTICS:

- Histologically confirmed adenocarcinoma of the prostate

- Progressive disease after a prior docetaxel-based regimen OR failed a prior
docetaxel-based regimen

- Hormone-refractory disease, meeting 1 of the following criteria:

- Radiologically measurable disease

- Prostate-specific antigen (PSA) progression* while on hormonal therapy (including
withdrawal from a direct antagonist) NOTE: *If the confirmatory PSA value is less
than the screening PSA value, then an additional test for rising PSA is required
to document progression

- Must have underwent prior surgical castration OR currently be on a luteinizing
hormone-releasing hormone agonist

PATIENT CHARACTERISTICS:

- ANC > 1,500/mm³

- Platelet count > 100,000/mm³

- Hemoglobin > 10 g/dL (in the absence of packed red blood cell transfusions within the
past 4 weeks)

- Creatinine < 2 mg/dL

- AST and ALT < 2 times upper limit of normal (ULN)

- Alkaline phosphatase < 2 times ULN

- Fertile patients must use effective double-method contraception during and for 1 month
after completion of study treatment

- No other malignancy within the past 5 years except basal cell carcinoma

- No clinically significant New York Heart Association class II-IV cardiovascular
disease

- No evidence of severe or uncontrolled systemic disease (e.g., unstable or
uncompensated respiratory, cardiac, hepatic, or renal disease)

- No unresolved chronic toxicity > grade 2 from prior anticancer therapy, with the
exception of alopecia

- No other significant clinical disorder or laboratory finding that would preclude study
participation

- No known severe hypersensitivity to gefitinib or any of the excipients of this product

- No evidence of clinically active interstitial lung disease

- Patients with chronic, stable radiographic changes who are asymptomatic are
eligible

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- At least 4 weeks since prior cytotoxic therapy

- At least 4 weeks since prior direct antagonists, including flutamide and nilutamide

- At least 6 weeks since prior bicalutamide

- At least 30 days since prior nonapproved or investigational drugs

- More than 4 weeks since prior palliative radiotherapy

- The irradiated lesion must not be used to assess response rate

- No prior gefitinib or etoposide

- No concurrent palliative radiotherapy

- No concurrent chemotherapeutic agents

- No concurrent phenytoin, carbamazepine, rifampin, barbiturates, or Hypericum
perforatum (St. John's wort)

- No concurrent hormones except antiandrogen therapy, steroids for adrenal failure,
hormones for nondisease-related conditions (e.g., insulin for diabetes), or
intermittent dexamethasone as an antiemetic

- No concurrent initiation of IV and/or oral bisphosphonates specifically for
symptomatic bone metastases