Patients who have no response to preoperative chemotherapy and no residual disease following
surgery on Regimen A are treated on Regimen B postoperatively.
The following acronyms are used:
DDD Mitotane, NSC-38721
DOX Doxorubicin, NSC-123127
VCR Vincristine, NSC-67574
VP-16 Etoposide, NSC-141540
Regimen A: 4-Drug Combination Chemotherapy followed by Surgery followed by 4-Drug
Combination Chemotherapy. DDD/DOX/VCR/VP-16; followed by surgical debulking; followed by
Regimen B: Single-Agent Chemotherapy. DDD.
This is a study of infusional doxorubicin, vincristine, and etoposide in combination with
daily oral mitotane in patients with adrenocortical cancer. Although mitotane has been used
extensively in adrenocortical cancer and has documented single agent activity, only limited
experience is available in the use of mitotane in combination with chemotherapy. In this
trial the primary reason for using mitotane is an attempt to enhance therapeutic efficacy,
based on its documented in-vitro activity as an antagonist of P-glycoprotein. The goal of
this study is to determine the efficacy of this therapy by treating patients who are
considered candidates for surgical resection at presentation or following a response to
therapy. Following chemotherapy, patients deemed surgical candidates can undergo surgical
resection with evaluation of response. Patients responding to chemotherapy will resume the
combination treatment after surgery. Patients who do not respond will be maintained on
single agent mitotane until it is deemed ineffective.
Biopsy-proven primary or recurrent adrenocortical carcinoma considered surgically
resectable at presentation or potentially resectable following an initial response to
Potentially resectable disease includes primary lesion, nodal metastases, and liver and
lung metastases if limited in size and number.
Patients for whom surgical resection is considered unlikely may be entered at the
discretion of the investigator.
Measurable disease at presentation required.
A life expectancy of at least 3 months and a performance status (Karnofsky scale) of 70
percent or greater.
Prior chemotherapy is allowed, however, the patient should not have received chemotherapy
four weeks before presentation.
Patients who have received prior doxorubicin may be enrolled provided they meet all other
entry criteria and have an ejection fraction greater than 40 percent determined by MUGA
Prior mitotane therapy is allowed. A dose of 3 gm/day should have been tolerated for at
least one week. Patients do not need to be off mitotane therapy prior to starting this
WBC greater 3,000/mm(3); Platelet count greater than 100,000/mm(3); Creatinine clearance
greater than 50 ml/min; bilirubin less than 1.5 mg/dl; serum transaminase less than 2
Patient should be a good surgical candidate.
Must sign an informed consent and be geographically accessible to return for follow up
No presence of a second malignancy, other than squamous cell carcinoma of the skin.
No active systemic infection.
Must not be currently receiving treatment which cannot be discontinued with the following
agents: diltiazem, nicardipine, phenothiazines, phenytoin, terfenadine or verapamil.
No positive serology for HIV.
No positive pregnancy test.