A phase II trial of combination chemotherapy and surgical resection for the treatment of metastatic adrenocortical carcinoma

作者：Jame Abraham, Susan Bakke, Ann Rutt, Beverly Meadows, Maria Merino, Richard H. Alexander, David S. Schrump, David B. Bartlett, Peter Choyke, Robert W. Robey, Elizabeth Hung, Seth M. Steinberg, Susan E. Bates, Tito Fojo · 发表于：Cancer · 年份：2002 · DOI：10.1002/cncr.10487 · 被引用次数：120 · 研究领域：Adrenal and Paraganglionic Tumors、Pituitary Gland Disorders and Treatments、Neuroblastoma Research and Treatments

BACKGROUND: Adrenocortical carcinoma (ACC) is rare, nearly always fatal, and to the authors' knowledge has few nonsurgical treatment options. Based on in vitro studies demonstrating the efficacy of mitotane as a P-glycoprotein (Pgp) antagonist, and expression of high levels of Pgp in ACC, the authors conducted a study of infusional doxorubicin, vincristine, and etoposide with oral mitotane +/- surgical resection in patients with metastatic ACC. METHODS: Thirty-six patients with metastatic ACC received daily oral mitotane (mean, 4.6 g/day) and 96-hour infusional doxorubicin (10 mg/m(2)/day), etoposide (75 mg/m(2)/day), and vincristine (0.4 mg/m(2)/day). Four responding patients (11%) underwent surgery. RESULTS: Thirty-five patients were evaluable; all had metastatic disease. Eleven patients had not undergone resection of the primary tumor. Approximately 53% of patients had functional tumors. A total of 190 cycles were administered to 36 patients. Responses were observed in 8 patients (22%): 1 complete, 4 partial, and 3 minor responses. The mean duration of response was 12.4 months. Using a landmark method, the median survival of patients who did not respond to chemotherapy was 11.6 months from a point 4 months after the initiation of therapy, whereas that of 8 patients who demonstrated a response to chemotherapy was 34.3 months from that same landmark. High levels of Pgp expression were documented in nine of nine tumors. Mitotane levels > 10 microg/mL, previously shown to anta...