Phase II evaluation of cisplatin and etoposide followed by mitotane at disease progression in patients with locally advanced or metastatic adrenocortical carcinoma - A Southwest Oncology Group study

BACKGROUND. A previous Southwest Oncology Group study demonstrated a 30% re sponse rate with the combination of cisplatin and mitotane in the treatment of patients with metastatic adrenocortical carcinoma. Several case reports suggested that the combination of etoposide and cisplatin may be an active regimen in this disease. Because of these reports of potential activity, t he authors conducted a Phase II trial evaluating the combination of etoposi de and cisplatin. Due to the lack of data regarding the objective response rates to mitotane, the authors planned to evaluate the response rate to mit otane after disease progression on etoposide and cisplatin in patients with no prior mitotane therapy. METHODS. Patients with advanced, unresectable, or metastatic adrenocortical carcinoma with objectively measurable disease or biochemical abnormalities received cisplatin, 50 mg/m(2), intravenously on Days 1 and 2, and etoposi de, 100 mg/m(2), on Days 1, 2, and 3. Cycles were repeated every 21 days. A t the time of disease progression, patients who had not previously received mitotane received 1000 mg orally 4 times a day along with cortisone acetat e and fludrocortisone acetate. RESULTS. Of the 47 patients entered onto the study, 45 were eligible. Nine patients had received mitotane previously and 36 had not. Objective respons es were noted in 11% of patients (5 of 45 patients) (95% confidence interva l, 3.7-24%). The median survival was 10 months. The most common to;dc effec ts were hematologic, gastrointestinal, and neurologic. Only 16 patients wit h no prior mitotane therapy went on to receive mitotane at the time of dise ase progression. An objective response was noted in 13% of patients (2 of 1 6 patients). The most common toxic effects were edema and gastrointestinal effects. CONCLUSIONS. The current study demonstrates that the combination of cisplat in and etoposide has minimal activity in advanced and metastatic adrenocort ical carcinoma and other treatment strategies are warranted. (C) 2000 Ameri can Cancer Society.