Protocol was closed due to slow accrual.

RATIONALE: Gefitinib may stop the growth of kidney cancer by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth. PEG-interferon alfa-2b may interfere with the growth of tumor cells and slow the growth of kidney cancer. Giving gefitinib together with PEG-interferon alfa-2b may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving gefitinib together with PEG-interferon alfa-2b works in treating patients with unresectable or metastatic kidney cancer.

OBJECTIVES:

Primary

• Determine the 6-month progression-free survival of patients with unresectable or metastatic renal cell carcinoma treated with gefitinib and PEG-interferon alfa-2b.

Secondary

• Determine the response rate (by RECIST criteria), duration of response, time to treatment failure, and overall survival of patients treated with this regimen.
• Assess toxicity and tolerability of this regimen in these patients.
• Determine the pre-treatment expression of the von Hippel-Lindau (VHL) protein, the epidermal growth factor receptor (EGFR), and p27, and correlate with response to treatment.
• Determine post-treatment alteration of EGFR and p27 expression in patients with tumors accessible for serial biopsy.
• Assess changes in EGFR levels in buccal epithelial cells in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive oral gefitinib once daily and PEG-interferon alfa-2b subcutaneously once weekly in weeks 1-6. Treatment repeats every 6 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with a partial response or stable disease after completion of course 2 continue to receive gefitinib alone as above in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 2 years.

PROJECTED ACCRUAL: A total of 39 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed renal cell carcinoma

  • Metastatic or advanced/unresectable disease

• Measurable or nonmeasurable disease as defined by RECIST criteria

• No uncontrolled brain metastases

  • Patients with adequately treated brain metastases who are not taking anticonvulsants and corticosteroids may be eligible

PATIENT CHARACTERISTICS:

• Karnofsky performance status 60-100%

• Life expectancy ≥ 12 weeks

• WBC ≥ 3,500/mm³

• Platelet count ≥ 100,000/mm³

• Absolute granulocyte count ≥ 1,500/mm³

• Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 50 mL/min

• Bilirubin ≤ 1.5 mg/dL

• AST ≤ 2 times upper limit of normal (ULN)

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or adequately treated stage I or II cancer from which the patient is currently in complete remission

• No known severe hypersensitivity to gefitinib or its excipients

• No incomplete healing from previous oncologic or other major surgery

• No unresolved chronic toxicity > grade 2 from previous anticancer therapy (except alopecia and anemia)

• No evidence of clinically active interstitial lung disease

  • Patients with chronic stable radiographic changes who are asymptomatic are eligible

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

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

PRIOR CONCURRENT THERAPY:

• More than 30 days since prior nonapproved or investigational drugs
• More than 6 weeks since prior aldesleukin or interferon and recovered
• At least 3 weeks since prior radiotherapy
• No prior gefitinib
• Prior chemotherapy or biological therapy allowed
• Prior or concurrent bisphosphonate therapy for bone metastases allowed
• No concurrent phenytoin, carbamazepine, rifampin, barbiturates, phenobarbital, or Hypericum perforatum (St. John's wort)
• No other concurrent agents specifically designed to inhibit the epidermal growth factor receptor (EGFR)
• No concurrent radiotherapy to measurable lesions

Adverse events were collected over a period of 38 months.

"Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.

Protocol was closed prior to the second stage of accrual (pegged at n = 24) due to slow accrual. The reason for the slow accrual was likely the availability of several new Food and Drug Administration approved targeted agents during the study period.