• Response rate (partial or complete) [ Designated as safety issue: No ]
• Progression-free survival [ Designated as safety issue: No ]

• Response rate (partial or complete)
• Progression-free survival

• Assessment of the extent of in vivo P-glycoprotein (Pgp) inhibition in CD56-positive cells as measured by CD56-positive cell assay with rhodamine [ Designated as safety issue: No ]
• In vivo imaging with 99mTc-sestamibi and assessment of Pgp inhibition [ Designated as safety issue: No ]
• Correlation of the pattern of gene expression found with the cDNA microarray with response and survival [ Designated as safety issue: No ]
• Correlation of Pgp expression as measured by quantitative polymerase chain reaction and immunohistochemistry with response [ Designated as safety issue: No ]

• Assessment of the extent of in vivo P-glycoprotein (Pgp) inhibition in CD56-positive cells as measured by CD56-positive cell assay with rhodamine
• In vivo imaging with 99mTc-sestamibi and assessment of Pgp inhibition
• Correlation of the pattern of gene expression found with the cDNA microarray with response and survival
• Correlation of Pgp expression as measured by quantitative polymerase chain reaction and immunohistochemistry with response

RATIONALE: Drugs used in chemotherapy, such as mitotane, doxorubicin, vincristine, and etoposide, work in different ways to stop tumor cells from dividing so they stop growing or die. Tariquidar may increase the effectiveness of chemotherapy drugs by making tumor cells more sensitive to the drugs. Giving chemotherapy combined with tariquidar before surgery may shrink the tumor so that it can be removed. Giving the drugs after surgery may kill any remaining tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining tariquidar with combination chemotherapy and surgery in treating patients who have recurrent, metastatic, or primary unresectable adrenocortical cancer.

OBJECTIVES:

Primary

• Compare response rate and progression-free survival of patients with recurrent, metastatic, or primary unresectable adrenocortical cancer treated with combination chemotherapy comprising tariquidar, mitotane, doxorubicin, vincristine, and etoposide and surgery vs historical controls treated with the same chemotherapy regimen but without tariquidar.
• Determine the overall survival of patients treated with this regimen.

Secondary

• Determine the safety of this regimen in these patients.
• Correlate DNA microarray analysis data with clinical presentation (including functional status of the tumor), response to therapy, and long-term clinical outcome in patients treated with this regimen.

OUTLINE: Patients receive oral mitotane daily beginning on day 1 (and continuing during entire treatment period), tariquidar IV over 30 minutes on days 1 and 3, and doxorubicin, vincristine, and etoposide IV continuously over 96 hours on days 1-4. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 2 additional treatment courses beyond CR.

Patients may undergo surgery, if possible, after study therapy. Patients without residual disease who respond to chemotherapy (administered prior to surgery) receive 2 additional courses of chemotherapy (as above) beginning 3 weeks after surgery. Patients with or without residual disease who do not respond to chemotherapy (administered prior to surgery) are removed from the study and may receive single-agent mitotane daily beginning as soon as medically indicated after surgery and continuing indefinitely. Patients with residual disease who respond to chemotherapy (administered prior to surgery) receive additional chemotherapy (as above) beginning as soon as medically indicated after surgery.

Patients are followed every 3-12 months for up to 7 years.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study within 3 years.

• Drug: doxorubicin hydrochloride
• Drug: etoposide
• Drug: mitotane
• Drug: tariquidar
• Drug: vincristine sulfate
• Procedure: adjuvant therapy
• Procedure: conventional surgery
• Procedure: neoadjuvant therapy

DISEASE CHARACTERISTICS:

• Histologically confirmed adrenocortical carcinoma

  • Recurrent, metastatic, or primary unresectable disease
• No tumors potentially curable by surgical excision alone
• Measurable disease at presentation
• No untreated brain metastases OR local treatment of brain metastases within the past 6 months

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 3 months

Hematopoietic

• Absolute neutrophil count at least 1,000/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN) (except for patients with Gilbert's syndrome)
• AST and ALT no greater than 3 times ULN

Renal

• Creatinine clearance at least 40 mL/min OR
• Creatinine no greater than 1.6 mg/dL

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• Ejection fraction at least 40% by MUGA, echocardiogram, or cardiac MRI for patients with a clinical history suggestive of systolic dysfunction

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 1 month after study participation
• No seizure disorder
• No psychiatric illness that would preclude study compliance
• No other uncontrolled illness that would preclude study participation
• No other malignancy within the past 2 years except squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)

• Prior mitotane allowed

  • Patients do not need to be off mitotane before starting this study

Endocrine therapy

• Not specified

Radiotherapy

• At least 4 weeks since prior radiotherapy

  • Must have sites of measurable disease that did not receive radiotherapy

Surgery

• Not specified

Other

• More than 4 weeks since prior experimental therapy

• No concurrent treatment with any of the following:

  • Diltiazem
  • Nicardipine
  • Phenothiazines
  • Phenytoin
  • Verapamil