{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T17:57:59Z","timestamp":1791136679237,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2002,4,25]],"date-time":"2002-04-25T00:00:00Z","timestamp":1019692800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2002,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>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\u2010glycoprotein (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 \u00b1 surgical resection in patients with metastatic ACC.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Thirty\u2010six patients with metastatic ACC received daily oral mitotane (mean, 4.6 g\/day) and 96\u2010hour infusional doxorubicin (10 mg\/m<jats:sup>2<\/jats:sup>\/day), etoposide (75 mg\/m<jats:sup>2<\/jats:sup>\/day), and vincristine (0.4 mg\/m<jats:sup>2<\/jats:sup>\/day). Four responding patients (11%) underwent surgery.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Thirty\u2010five 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 &gt; 10 \u03bcg\/mL, previously shown to antagonize Pgp in vitro, were achieved in 25 of 36 patients (69%). However, rhodamine efflux from CD56\u2010positive cells was not impaired, suggesting poor in vivo Pgp inhibition. The predominant Grade 3\/4 toxicity (according to the Common Toxicity Criteria of the National Cancer Institute) was neutropenia in 66% of cycles; however, fever occurred in only 3% of cycles. Daily mitotane was associated with Grade 1\/2 nausea, diarrhea, fatigue, and neuropsychiatric changes in 31 of 36 patients (86%).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Using a combination regimen of daily mitotane with infusional doxorubicin, vincristine, and etoposide in patients with metastatic ACC, responses were observed in 22% of patients. The superiority of this combination over single\u2010agent mitotane is uncertain. The side effects of mitotane made treatment difficult. More effective Pgp antagonists are needed. Cancer 2002;94:2333\u201343. \u00a9 2002 American Cancer Society.<\/jats:p><jats:p>DOI 10.1002\/cncr.10487<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.10487","type":"journal-article","created":{"date-parts":[[2004,10,27]],"date-time":"2004-10-27T03:57:47Z","timestamp":1098849467000},"page":"2333-2343","source":"Crossref","is-referenced-by-count":100,"title":["A phase II trial of combination chemotherapy and surgical resection for the treatment of metastatic adrenocortical 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