Anastrozole & ZD1839 Compared With Fulvestrant & ZD1839 in Postmenopausal Women w/ Metastatic Breast Cancer

Inclusion criteria:

• Histologically confirmed adenocarcinoma of the breast (Recurrent or metastatic disease)
• Measurable disease
• Patients with available tissue blocks from either the primary or metastatic site must submit the tissue for epidermal growth factor receptor analysis
• Estrogen and/or progesterone receptor positive
• Age>=18
• Female

• Postmenopausal, defined by 1 of the following:

  • Prior bilateral oophorectomy or bilateral ovarian irradiation
  • No menstrual period for at least 12 months

NOTE: If age 55 and under and on tamoxifen within the past 6 months, must have an estradiol level in the postmenopausal range

• ECOG performance status of 0-2

• Adequate hematopoietic, hepatic, renal functions defined by the following within 2 weeks prior to randomization:

  • Neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Bilirubin no greater than 1.25 times upper limit of normal (ULN)
  • Serum glutamic-pyruvic transaminase (ALT) and Serum glutamic-oxaloacetic (AST) no greater than 2.5 times ULN (5 times ULN if liver metastases are present)
  • International normalized ratio of prothrombin time (INR), prothrombin time (PT), and partial thromboplastin time (PTT) normal
  • Creatinine clearance at least 30 mL/min
• More than 3 weeks since prior trastuzumab (Herceptin®)
• More than 3 weeks since prior chemotherapy
• More than 3 months since prior luteinizing hormone-releasing hormone agonists or antagonists (patients 55 years old and under)
• Recovered from prior radiotherapy

• Concurrent radiotherapy to painful sites of bony disease or areas of impending fracture is allowed provided the following conditions are met:

  • Therapy was initiated prior to study entry
  • Sites of measurable disease outside the radiotherapy port are available for disease evaluation
• Concurrent bisphosphonates for hypercalcemia or bone metastases are allowed

Exclusion Criteria:

• Pregnant or nursing
• Untreated ocular inflammation or infection
• Medical or psychiatric condition that would preclude study compliance, ability to give informed consent, or assessment of response or anticipated toxic effects
• History of central nervous system (CNS) metastasis
• Other invasive malignancies within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• Contraindication to intramuscular injections
• More than 2 prior chemotherapy regimens for metastatic disease
• Prior hormonal therapy for metastatic disease
• Prior estrogen receptor down-regulators (e.g., fulvestrant) in the adjuvant setting
• Prior aromatase inhibitors (e.g., anastrozole, letrozole, exemestane, or aminoglutethimide) in the adjuvant setting
• Prior agents that target epidermal growth factor receptors
• Other concurrent hormonal therapy
• Concurrent chemotherapy
• Concurrent trastuzumab
• Concurrent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors (e.g., ketoconazole, erythromycin, or verapamil)
• Concurrent anticoagulants, except for thrombotic events in patients in arm I
• Concurrent medications that would alter the pharmacokinetics of gefitinib (e.g., phenytoin, carbamazepine, phenobarbital, rifampin, Hypericum perforatum [St. John's wort], oxcarbazepine, rifapentine, modafinil, and griseofulvin)