BACKGROUND: Adrenocortical carcinoma is a rare cancer that has a poor response to cytotoxic treatment. METHODS: We randomly assigned 304 patients with advanced adrenocortical carcinoma to receive mitotane plus either a combination of etoposide (100 mg per square meter of body-surface area on days 2 to 4), doxorubicin (40 mg per square meter on day 1), and cisplatin (40 mg per square meter on days 3 and 4) (EDP) every 4 weeks or streptozocin (streptozotocin) (1 g on days 1 to 5 in cycle 1; 2 g on day 1 in subsequent cycles) every 3 weeks. Patients with disease progression received the alternative regimen as second-line therapy. The primary end point was overall survival. RESULTS: For first-line therapy, patients in the EDP-mitotane group had a significantly higher response rate than those in the streptozocin-mitotane group (23.2% vs. 9.2%, P<0.001) and longer median progression-free survival (5.0 months vs. 2.1 months; hazard ratio, 0.55; 95% confidence interval [CI], 0.43 to 0.69; P<0.001); there was no significant between-group difference in overall survival (14.8 months and 12.0 months, respectively; hazard ratio, 0.79; 95% CI, 0.61 to 1.02; P = 0.07). Among the 185 patients who received the alternative regimen as second-line therapy, the median duration of progression-free survival was 5.6 months in the EDP-mitotane group and 2.2 months in the streptozocin-mitotane group. Patients who did not receive the alternative second-line therapy had better overall survival with first-line EDP plus mitotane (17.1 month) than with streptozocin plus mitotane (4.7 months). Rates of serious adverse events did not differ significantly between treatments. CONCLUSIONS: Rates of response and progression-free survival were significantly better with EDP plus mitotane than with streptozocin plus mitotane as first-line therapy, with similar rates of toxic events, although there was no significant difference in overall survival. (Funded by the Swedish Research Council and others; FIRM-ACT ClinicalTrials.gov number, NCT00094497.) Copyright © 2012 Massachusetts Medical Society.
Combination chemotherapy in advanced adrenocortical carcinoma / M., Fassnacht; M., Terzolo; B., Allolio; E., Baudin; H., Haak; A., Berruti; S., Welin; C., Schade Brittinger; A., Lacroix; B., Jarzab; H., Sorbye; D. J., Torpy; V., Stepan; D. E., Schteingart; W., Arlt; M., Kroiss; S., Leboulleux; P., Sperone; A., Sundin; I., Hermsen; S., Hahner; H. S., Willenberg; A., Tabarin; M., Quinkler; C., De La Fouchardiere; M., Schlumberger; F., Mantero; D., Weismann; F., Beuschlein; H., Gelderblom; H., Wilmink; M., Sender; M., Edgerly; W., Kenn; T., Fojo; H. H., Muller; B., Skogseid; M., Haaf; S., Johanssen; A. C., Koschker; K., Laubner; S., Sbiera; J., Schiemann; S., Wortmann; M., Haase; M., Schott; M., Möhlig; K., Zopf; N., Reisch; M., Betz; M., Reincke; B., Isermann; S., Bornstein; C., Fottner; A., Bose; S., Petersenn; H., Leitolf; S., Klose; H., Wolf; C., Chougnet; J., More; M. L., Nunes; J. P., Droz; P., Nicolli; O., Chabre; A., Clergeot; F., Schillo; A., Penfornis; C., Do Cao; F., Goldwasser; P., Rodien; A., Ferrero; P., Perotti; Anna P., Cicala Mv; S., Della Casa; M., Mannelli; V., Piccini; M. W., Dercksen; J. A., Romijn; J., Ouwerkerk; J. H., Devries; B., Eriksson; E. T., Janson; D., Granberg; K., Oberg; H., Ahlman; M., Garkavij; N., Wall; U., Falkmer; G., Hammer; H. J., Olney; I., Bourdeau; L., Bourque; S., Szpak Ulczok; M., Jarzab; H., Holte; A., Fossa; F., Ploner; U., Mansmann; H. J., Schmoll; B., Simonsson; Toscano, Vincenzo. - In: THE NEW ENGLAND JOURNAL OF MEDICINE. - ISSN 0028-4793. - STAMPA. - 366:23(2012), pp. 2189-2197. [10.1056/nejmoa1200966]
Combination chemotherapy in advanced adrenocortical carcinoma
TOSCANO, Vincenzo
2012
Abstract
BACKGROUND: Adrenocortical carcinoma is a rare cancer that has a poor response to cytotoxic treatment. METHODS: We randomly assigned 304 patients with advanced adrenocortical carcinoma to receive mitotane plus either a combination of etoposide (100 mg per square meter of body-surface area on days 2 to 4), doxorubicin (40 mg per square meter on day 1), and cisplatin (40 mg per square meter on days 3 and 4) (EDP) every 4 weeks or streptozocin (streptozotocin) (1 g on days 1 to 5 in cycle 1; 2 g on day 1 in subsequent cycles) every 3 weeks. Patients with disease progression received the alternative regimen as second-line therapy. The primary end point was overall survival. RESULTS: For first-line therapy, patients in the EDP-mitotane group had a significantly higher response rate than those in the streptozocin-mitotane group (23.2% vs. 9.2%, P<0.001) and longer median progression-free survival (5.0 months vs. 2.1 months; hazard ratio, 0.55; 95% confidence interval [CI], 0.43 to 0.69; P<0.001); there was no significant between-group difference in overall survival (14.8 months and 12.0 months, respectively; hazard ratio, 0.79; 95% CI, 0.61 to 1.02; P = 0.07). Among the 185 patients who received the alternative regimen as second-line therapy, the median duration of progression-free survival was 5.6 months in the EDP-mitotane group and 2.2 months in the streptozocin-mitotane group. Patients who did not receive the alternative second-line therapy had better overall survival with first-line EDP plus mitotane (17.1 month) than with streptozocin plus mitotane (4.7 months). Rates of serious adverse events did not differ significantly between treatments. CONCLUSIONS: Rates of response and progression-free survival were significantly better with EDP plus mitotane than with streptozocin plus mitotane as first-line therapy, with similar rates of toxic events, although there was no significant difference in overall survival. (Funded by the Swedish Research Council and others; FIRM-ACT ClinicalTrials.gov number, NCT00094497.) Copyright © 2012 Massachusetts Medical Society.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
