Long-Term Outcomes of Adjuvant Mitotane Therapy in Patients With Radically Resected Adrenocortical Carcinoma.
BACKGROUND
In 2007, a retrospective case-control study provided evidence that adjuvant mitotane prolongs recurrence-free survival (RFS) in patients with radically resected adrenocortical carcinoma (ACC).


OBJECTIVE
We aimed to confirm the prognostic role of adjuvant mitotane in the same series after 9 additional years of follow-up.


METHODS
One hundred sixty-two ACC patients who did not recur or die after a landmark period of 3 months were considered. Forty-seven patients were enrolled in four Italian centers where adjuvant mitotane was routinely recommended (mitotane group), 45 patients in four Italian centers where no adjuvant strategy was undertaken (control group 1), and 70 German patients left untreated after surgery (control group 2).


METHODS
The primary aim was RFS, the secondary was overall survival.


RESULTS
An increased risk of recurrence was found in both control cohorts [group 1: hazard ratio (HR) = 2.98; 95% confidence interval (CI), 1.75 to 5.09; P < 0.0001; group 2: HR = 2.61; 95% CI, 1.56 to 4.36; P < 0.0001] compared with the mitotane group. The risk of death was higher in control group 1 (HR = 2.03; 95% CI, 1.17 to 3.51; P = 0.011) but not in control group 2 (HR = 1.60; 95% CI, 0.94 to 2.74; P = 0.083), which had better prognostic factors and more aggressive treatment of recurrences than control group 1. The benefit of adjuvant mitotane on RFS was observed regardless of the hormone secretory status.


CONCLUSIONS
Adjuvant mitotane is associated with prolonged RFS, without any apparent influence by the tumor secretory status. The retrospective nature of the study is a major limitation.
Medical Oncology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, and.
Alfredo
A
Berruti
Medical Oncology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, and.
Salvatore
S
Grisanti
Comprehensive Cancer Center Mainfranken, and.
Alina
A
Pulzer
Medical Oncology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, and.
Mélanie
M
Claps
Internal Medicine 1, Department of Clinical and Biological Sciences, San Luigi Hospital.
Fulvia
F
Daffara
Endocrine Unit, Department of Medical Specialties, Ospedale Niguarda Cà Granda, 20162 Milano, Italy.
Paola
P
Loli
Department of Experimental and Clinical Biomedical Sciences "Mario Serio," University of Florence, 50121 Florence, Italy.
Massimo
M
Mannelli
Endocrinology Unit, Department of Medicine, Padova University Hospital, 35122 Padova, Italy.
Marco
M
Boscaro
Oncological Endocrinology Unit, Department of Medical Sciences, and.
Emanuela
E
Arvat
Surgical Clinic, Department of Medical and Surgical Sciences, University of Brescia, 25123 Brescia, Italy.
Guido
G
Tiberio
Department of Internal Medicine I, Division of Endocrinology and Diabetology, University Hospital, University of Würzburg, 97070 Würzburg, Germany.
Stefanie
S
Hahner
Internal Medicine 1, Department of Clinical and Biological Sciences, San Luigi Hospital.
Barbara
B
Zaggia
Urology and.
Francesco
F
Porpiglia
Pathology Units, Department of Oncology, University of Turin, 10129 Torino, Italy.
Marco
M
Volante
Comprehensive Cancer Center Mainfranken, and.|Department of Internal Medicine I, Division of Endocrinology and Diabetology, University Hospital, University of Würzburg, 97070 Würzburg, Germany.
Martin
M
Fassnacht
Internal Medicine 1, Department of Clinical and Biological Sciences, San Luigi Hospital.
Massimo
M
Terzolo
D000293:Adolescent; D000306:Adrenal Cortex Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D000315:Adrenalectomy / Q000379:methods; D018268:Adrenocortical Carcinoma / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D016022:Case-Control Studies; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008939:Mitotane / Q000627:therapeutic use*; D009364:Neoplasm Recurrence, Local / Q000401:mortality; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
D018931:Antineoplastic Agents, Hormonal; D008939:Mitotane