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

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.