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

• 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 undergone prior surgical castration OR currently be on a luteinizing hormone-releasing hormone agonistANC > 1,500/mm³Platelet count > 100,000/mm³Hemoglobin > 10 g/dL (in the absence of packed red blood cell transfusions within the past 4 weeks)Creatinine \< 2 mg/dLAST and ALT \< 2 times upper limit of normal (ULN)Alkaline phosphatase \< 2 times ULNFertile patients must use effective double-method contraception during and for 1 month after completion of study treatmentAt 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 o The irradiated lesion must not be used to assess response rate

Exclusion Criteria:

• 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

  o Asymptomatic Patients with chronic, stable radiographic changes are eligible

• 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