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Original Article
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Volume 356:2372-2380 June 7, 2007 Number 23
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Adjuvant Mitotane Treatment for Adrenocortical Carcinoma
Massimo Terzolo, M.D., Alberto Angeli, M.D., Martin Fassnacht, M.D., Fulvia Daffara, M.D., Libuse Tauchmanova, M.D., Pier Antonio Conton, M.D., Ruth Rossetto, M.D., Lisa Buci, M.D., Paola Sperone, M.D., Erika Grossrubatscher, M.D., Giuseppe Reimondo, M.D., Enrico Bollito, M.D., Mauro Papotti, M.D., Wolfgang Saeger, M.D., Stefanie Hahner, M.D., Ann-Cathrin Koschker, M.D., Emanuela Arvat, M.D., Bruno Ambrosi, M.D., Paola Loli, M.D., Gaetano Lombardi, M.D., Massimo Mannelli, M.D., Paolo Bruzzi, M.D., Franco Mantero, M.D., Bruno Allolio, M.D., Luigi Dogliotti, M.D., and Alfredo Berruti, M.D.

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ABSTRACT

Background Adrenocortical carcinoma is a rare neoplasm characterized by a high risk of recurrence after radical resection. Whether the use of mitotane is beneficial as an adjuvant treatment has been controversial. Our aim was to evaluate the efficacy of adjuvant mitotane in prolonging recurrence-free survival.

Methods We performed a retrospective analysis involving 177 patients with adrenocortical cancer who had undergone radical surgery at 8 centers in Italy and 47 centers in Germany between 1985 and 2005. Adjuvant mitotane was administered to 47 Italian patients after radical surgery (mitotane group), whereas 55 Italian patients and 75 German patients (control groups 1 and 2, respectively) did not receive adjuvant treatment after surgery.

Results Baseline features in the mitotane group and the control group from Italy were similar; the German patients were significantly older (P=0.03) and had more stage I or II adrenocortical carcinomas (P=0.02) than did patients in the mitotane group. Recurrence-free survival was significantly prolonged in the mitotane group, as compared with the two control groups (median recurrence-free survival, 42 months, as compared with 10 months in control group 1 and 25 months in control group 2). Hazard ratios for recurrence were 2.91 (95% confidence interval [CI], 1.77 to 4.78; P<0.001) and 1.97 (95% CI, 1.21 to 3.20; P=0.005), respectively. Multivariate analysis indicated that mitotane treatment had a significant advantage for recurrence-free survival. Adverse events associated with mitotane were mainly of grade 1 or 2, but temporary dose reduction was needed in 13% of patients.

Conclusions Adjuvant mitotane may prolong recurrence-free survival in patients with radically resected adrenocortical carcinoma.


Source Information

From the Università di Torino, Turin, Italy (M.T., A.A., F.D., R.R., P.S., G.R., E.B., M.P., E.A., L.D., A.B.); University of Würzburg, Würzburg, Germany (M.F., S.H., A.-C.K., B. Allolio); Università Federico II di Napoli, Naples, Italy (L.T., G.L.); Università di Padova, Padua, Italy (P.A.C., F.M.); Università di Firenze, Florence, Italy (L.B., M.M.); Ospedale Niguarda Milano (E.G., P.L.) and Università di Milano (B. Ambrosi) — both in Milan; Institute of Pathology, Marienkrankenhaus, Hamburg, Germany (W.S.); and Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy (P.B.).

Address reprint requests to Dr. Terzolo, Medicina Interna I, A.S.O. San Luigi, Regione Gonzole 10, 10043 Orbassano, Italy, or at terzolo{at}usa.net.

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Related Letters:

Adjuvant Mitotane in Adrenocortical Carcinoma
Bertherat J., Coste J., Bertagna X., Dickstein G., Shechner C., Nativ O., Lee J. E., Machens A., Dralle H., Terzolo M., Fassnacht M., Berruti A.
Extract | Full Text | PDF  
N Engl J Med 2007; 357:1256-1259, Sep 20, 2007. Correspondence

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