• Ratio of dendritic cells (DC) to circulating immature cells (ImC) before and after treatment [ Designated as safety issue: No ]
• In vitro immune response assays to tetanus toxoid and influenza virus peptide before and after treatment [ Designated as safety issue: No ]

• Ratio of dendritic cells (DC) to circulating immature cells (ImC) before and after treatment
• In vitro immune response assays to tetanus toxoid and influenza virus peptide before and after treatment

• Frequency of treatment-related side effects [ Designated as safety issue: Yes ]
• Clinical objective response [ Designated as safety issue: No ]
• Progression-free survival [ Designated as safety issue: No ]
• Correlation of DC:ImC ratio with clinical objective response [ Designated as safety issue: No ]
• Correlation of the extent of change of the DC:ImC ratio with tretinoin dose and tretinoin blood levels [ Designated as safety issue: No ]

• Frequency of treatment-related side effects
• Clinical objective response
• Progression-free survival
• Correlation of DC:ImC ratio with clinical objective response
• Correlation of the extent of change of the DC:ImC ratio with tretinoin dose and tretinoin blood levels

RATIONALE: Tretinoin may help cells that are involved in the body's immune response to work better. Interleukin-2 may stimulate the white blood cells to kill kidney cancer cells. Giving tretinoin together with interleukin-2 may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying how well giving three different doses of tretinoin together with interleukin-2 works in treating patients with stage IV kidney cancer.

OBJECTIVES:

Primary

• Determine the ratio of dendritic cells (DC) to circulating immature cells (ImC) before and after treatment with 3 different doses of tretinoin in patients with stage IV renal cell cancer.
• Assess in vitro immune response assays to tetanus toxoid and influenza virus peptide before and after treatment with tretinoin and interleukin-2 in these patients.

Secondary

• Determine the frequency of treatment-related side effects in these patients.
• Determine clinical objective response and progression-free survival of patients treated with this regimen.
• Correlate DC:ImC ratio with clinical objective response in patients treated with this regimen.
• Correlate the extent of change of the DC:ImC ratio with tretinoin dose and tretinoin blood levels in these patients.

OUTLINE: This is a randomized, open-label study. Specimens are stratified according to patient prognostic factors, tumor bulk, and extent of dendritic cell to circulating immature cell ratio derangement. Patients are randomized to 1 of 3 tretinoin doses.

Patients receive oral tretinoin three times daily on days 1-7 of week 1. Patients then receive interleukin-2 subcutaneously on days 1-5 of weeks 3-8. Treatment repeats every 10-11 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed for up to 2 years.

PROJECTED ACCRUAL: A total of 27-36 patients (9-12 per treatment arm) will be accrued for this study within 2 years.

• Biological: aldesleukin
• Drug: tretinoin

DISEASE CHARACTERISTICS:

• Histologically confirmed renal cell cancer

  • Stage IV disease
  • Histology with clear cell component
• Metastatic OR incompletely resected disease
• Non-measurable disease allowed

• Underwent complete or partial nephrectomy more than 90 days ago

  • No unresected primary cancer

• No more than 2 of the following adverse factors:

  • Hemoglobin < 10.0 g/dL
  • Corrected calcium > upper limit of normal (ULN)
  • Lactic dehydrogenase > 1.5 times ULN
  • ECOG performance status 2
• Brain metastasis allowed provided more than 90 days of clinical and radiologic stability after the end of its active treatment

PATIENT CHARACTERISTICS:

Age

• Over 18

Performance status

• See Disease Characteristics
• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

Hepatic

• See Disease Characteristics
• SGOT < 3 times normal
• Bilirubin < 2 times normal

Renal

• See Disease Characteristics
• Creatinine clearance > 40 mL/min

Cardiovascular

• None of the following cardiovascular conditions within the past year:

  • Uncontrolled hypertension
  • Myocardial infarction
  • Unstable angina
  • New York Heart Association class II-IV congestive heart failure
  • Serious cardiac arrhythmia requiring medication
  • Class II-IV peripheral vascular disease within the past year
  • Other clinically significant cardiovascular disease

Immunologic

• No history of immunodeficiency disease
• No HIV infection
• No ongoing serious infection

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use two methods of effective contraception during and for 1 month (for women) or 6 months (for men) after study treatment
• Other prior malignancy allowed provided there is no evidence of active disease
• No other medical contraindication to tretinoin or interleukin-2
• No serious non-healing wound, ulcer, or bone fracture

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 60 days since prior immunotherapy

Chemotherapy

• At least 60 days since prior cytotoxic chemotherapy

Endocrine therapy

• See Radiotherapy
• No prior corticosteroids at > physiologic replacement doses for > 3 days within the past 90 days
• Concurrent tamoxifen, toremifene, megestrol, or gonadotropin-releasing hormone agonists allowed
• Concurrent inhaled steroids allowed

Radiotherapy

• More than 7 days since prior external-beam radiotherapy

  • No steroid requirement during radiotherapy

Surgery

• See Disease Characteristics
• At least 30 days since other prior debulking surgery

Other

• Prior adjuvant therapy for resected, synchronous stage IV disease allowed

• Prior adjuvant therapy allowed

  • Study therapy is not to be used as adjuvant therapy for completely resected late (> 1 year until identification) solitary site of disease metastasis or non-metastatic disease
• No prior participation in this clinical study
• At least 60 days since other prior anticancer drugs
• Concurrent seizure medication allowed