OBJECTIVES:

• Compare the efficacy of 2 different doses of ZD 1839, in terms of objective response, PSA response, and duration of response, in patients with hormone-refractory adenocarcinoma of the prostate.
• Compare the tolerability and quantitative toxicity of these regimens in these patients.
• Determine whether there is an association between any response or stable disease and clinical benefit as assessed by changes in quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to measurable disease (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral, low-dose ZD 1839 twice daily on day 1 and once daily on days 2-28 during course 1 and then once daily on days 1-28 during subsequent courses.
• Arm II: Patients receive oral, high-dose ZD 1839 as in arm I. Treatment in both arms continues every 4 weeks in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, at the end of each course during study, and then at 4 weeks after study.

Patients with stable or responding disease are followed at 4 weeks and then every 3 months until disease progression. All other patients are followed at 4 weeks only.

PROJECTED ACCRUAL: A total of 30-60 patients (15-30 per treatment arm) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the prostate
• PSA at least 20 ng/mL at study entry

• Must have documented evidence of disease progression, defined by 1 of the following conditions:

  • Rising PSA documented after discontinuation of peripheral antiandrogens

    • Minimum evidence of progression is a 25% increase in PSA over the reference value, provided that the increase is at least 5 ng/mL

      • Must have a first increase in PSA documented at least 1 week after the reference value and a second increase in PSA documented at least 1 week after the first increase
  • Progressive measurable disease during androgen ablative therapy (including medical or surgical castration)
• Castrate level (no greater than 50 ng/mL) of testosterone required if receiving medical androgen-ablative therapy at study entry
• Concurrent luteinizing hormone-releasing hormone agonist therapy required if receiving this medication at study entry

PATIENT CHARACTERISTICS:

Age:

• 16 and over

Performance status:

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Absolute granulocyte count at least 1,500/mm3
• Platelet count at least 100,000/mm3

Hepatic:

• Bilirubin no greater than 2 times upper limit of normal (ULN)
• AST/ALT no greater than 2.5 times ULN (5 times ULN if documented liver metastases)

Renal:

• Creatinine no greater than 2 times ULN

Other:

• No other malignancy within the past 5 years
• No active uncontrolled bacterial, fungal, or viral infection
• No significant neurological disorder that would preclude informed consent
• No other serious illness or medical condition that would preclude study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Concurrent epoetin alfa allowed

Chemotherapy:

• No prior chemotherapy
• No concurrent cytotoxic therapy

Endocrine therapy:

• See Disease Characteristics
• At least 4 weeks since prior peripheral antiandrogens (6 weeks for bicalutamide)
• Concurrent steroids allowed if on stable dose for at least 4 weeks before study and no dose increase planned

Radiotherapy:

• At least 4 weeks since prior radiotherapy except low-dose, nonmyelosuppressive radiotherapy approved by the National Cancer Institute of Canada, Clinical Trials Group

Surgery:

• See Disease Characteristics
• No concurrent ophthalmic surgery

Other:

• No prior investigational agents
• No other concurrent investigational therapy
• No concurrent ketoconazole
• No concurrent high-dose narcotic therapy for pain (e.g., morphine equivalent dose more than 60 mg/day)
• Concurrent bisphosphonates allowed