Inclusion Criteria:

• Histologically confirmed diagnosis of adrenocortical carcinoma
• Locally advanced or metastatic disease not amenable to radical surgery resection (Stage III-IV)
• Radiologically monitorable disease
• ECOG performance status 0-2
• Life expectancy > 3 months
• Age ≥18 years
• Adequate bone marrow reserve (neutrophils > 1500/mm3 and platelets > 100,000/mm3)
• Effective contraception in pre-menopausal female and male patients
• Patient's written informed consent
• Ability to comply with the protocol procedures (including availability for follow-up visits)
• Previous palliative surgery, radiotherapy or radiofrequency ablation is acceptable as long as radiologically monitorable disease is verifiable afterwards.

Exclusion Criteria:

• History of prior malignancy, except for cured non-melanoma skin cancer, curatively in situ cervical carcinoma, or other cancers treated with no evidence of disease for at least five years.
• Previous cytotoxic chemotherapy for adrenocortical carcinoma
• Renal insufficiency (serum creatinine ≥2 mg/dl or creatinine clearance ≤ 60 ml/min)
• Hepatic insufficiency (serum bilirubin ≥2 x the institutional upper limit of normal range and/or serum transaminases ≥ 3 x the institutional upper limit of normal range; exception: in patients on mitotane, transaminase levels up to 5 x the institutional upper limit of normal range are acceptable)
• Pregnancy or breast feeding
• Known hypersensitivity to any drug included in the treatment protocol
• Presence of active infection
• Any other severe clinical condition that in the judgment of the local investigator would place the patient at undue risk or interfere with the study completion
• Current treatment with other experimental drugs and/or previous participation in clinical trials with other experimental agents for adrenocortical carcinoma