Etoposide, doxorubicin and cisplatin plus mitotane in the treatment of advanced adrenocortical carcinoma: a large prospective phase II trial.
To investigate the activity of etoposide, doxorubicin, and cisplatin plus mitotane in the management of advanced adrenocortical carcinoma (ACC) patients, 72 patients with measurable disease not amenable to radical surgery were enrolled in a prospective, multicenter phase II trial. EDP schedule (etoposide 100 mg/m(2) on days 5-7, doxorubicin 20 mg/m(2) on days 1 and 8, and cisplatin 40 mg/m(2) on days 1 and 9) was administered intravenously every 4 weeks. Concomitantly, patients were given up to 4 g/day of oral mitotane. Five patients achieved a complete response and 30 a partial response, for an overall response rate of 48.6% (95% CI: 37.1-60.3). Median time to progression in responding patients was 18 months. The EDP regimen was well tolerated, leukopenia being the dose limiting toxicity. One toxic related death due to septic shock, however, was registered. Radical surgical resection of residual disease after chemotherapy was performed in 10 patients. The overall survival of patients attaining a disease free status (clinical complete responders+radically resected) was significantly higher than that of patients with partial response or no response (P<0.002). Androgen secretion was associated with long survival, while glucocorticoid secretion was associated with poor prognosis both in univariate and multivariate analysis. In conclusion, EDP plus mitotane is an active and manageable combination scheme for ACC patients. Surgical resection of residual disease subsequent to chemotherapy leads to a more favourable outcome. The natural history of the disease is significantly influenced by the secretory status of the tumor.
Berruti
Alfredo
A
Oncologia Medica, Università di Torino, Azienda Ospedaliera San Luigi, Regione Gonzole 10 10043 Orbassano, Torino, Italy.
Terzolo
Massimo
M
Sperone
Paola
P
Pia
Anna
A
Della Casa
Silvia
S
Gross
David J
DJ
Carnaghi
Carlo
C
Casali
Paolo
P
Porpiglia
Francesco
F
Mantero
Franco
F
Reimondo
Giuseppe
G
Angeli
Alberto
A
Dogliotti
Luigi
L
D000293:Adolescent; D000306:Adrenal Cortex Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D008939:Mitotane / Q000008:administration & dosage; D009367:Neoplasm Staging; D016019:Survival Analysis; D013997:Time Factors
D005047:Etoposide; D008939:Mitotane; D004317:Doxorubicin; D002945:Cisplatin