Adjuvant mitotane treatment for adrenocortical carcinoma.
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.
Terzolo
Massimo
M
Università di Torino, Turin, Italy. terzolo@usa.net
Angeli
Alberto
A
Fassnacht
Martin
M
Daffara
Fulvia
F
Tauchmanova
Libuse
L
Conton
Pier Antonio
PA
Rossetto
Ruth
R
Buci
Lisa
L
Sperone
Paola
P
Grossrubatscher
Erika
E
Reimondo
Giuseppe
G
Bollito
Enrico
E
Papotti
Mauro
M
Saeger
Wolfgang
W
Hahner
Stefanie
S
Koschker
Ann-Cathrin
AC
Arvat
Emanuela
E
Ambrosi
Bruno
B
Loli
Paola
P
Lombardi
Gaetano
G
Mannelli
Massimo
M
Bruzzi
Paolo
P
Mantero
Franco
F
Allolio
Bruno
B
Dogliotti
Luigi
L
Berruti
Alfredo
A
D000306:Adrenal Cortex Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D018268:Adrenocortical Carcinoma / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D006801:Humans; D008939:Mitotane / Q000009:adverse effects / Q000627:therapeutic use*; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000517:prevention & control; D012189:Retrospective Studies; D016019:Survival Analysis
D018931:Antineoplastic Agents, Hormonal; D008939:Mitotane