Combination chemotherapy in advanced adrenocortical carcinoma

Martin Fassnacht; Massimo Terzolo; Bruno Allolio; Eric Baudin; Harm Haak; Alfredo Berruti; Staffan Welin; Carmen Schade-Brittinger; André Lacroix; Barbara Jarzab; Halfdan Sorbye; David J Torpy; Vinzenz Stepan; David E Schteingart; Wiebke Arlt; Matthias Kroiss; Sophie Leboulleux; Paola Sperone; Anders Sundin; Ilse Hermsen; Stefanie Hahner; Holger S Willenberg; Antoine Tabarin; Marcus Quinkler; Christelle de la Fouchardière; Martin Schlumberger; Franco Mantero; Dirk Weismann; Felix Beuschlein; Hans Gelderblom; Hanneke Wilmink; Monica Sender; Maureen Edgerly; Werner Kenn; Tito Fojo; Hans-Helge Müller; Britt Skogseid; FIRM-ACT Study Group

doi:10.1056/NEJMoa1200966

Combination chemotherapy in advanced adrenocortical carcinoma

Martin Fassnacht, Massimo Terzolo, Bruno Allolio, Eric Baudin, Harm Haak, Alfredo Berruti, Staffan Welin, Carmen Schade-Brittinger, André Lacroix, Barbara Jarzab, Halfdan Sorbye, David J Torpy, Vinzenz Stepan, David E Schteingart, Wiebke Arlt, Matthias Kroiss, Sophie Leboulleux, Paola Sperone, Anders Sundin, Ilse HermsenStefanie Hahner, Holger S Willenberg, Antoine Tabarin, Marcus Quinkler, Christelle de la Fouchardière, Martin Schlumberger, Franco Mantero, Dirk Weismann, Felix Beuschlein, Hans Gelderblom, Hanneke Wilmink, Monica Sender, Maureen Edgerly, Werner Kenn, Tito Fojo, Hans-Helge Müller, Britt Skogseid, FIRM-ACT Study Group

Metabolism and Systems Science

Research output: Contribution to journal › Article › peer-review

444 Citations (Scopus)

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.).

Original language	English
Pages (from-to)	2189-97
Number of pages	9
Journal	The New England Journal of Medicine
Volume	366
Issue number	23
DOIs	https://doi.org/10.1056/NEJMoa1200966
Publication status	Published - 7 Jun 2012

Keywords

Adrenal Cortex Neoplasms
Adrenocortical Carcinoma
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols
Cisplatin
Disease-Free Survival
Doxorubicin
Etoposide
Female
Humans
Intention to Treat Analysis
Kaplan-Meier Estimate
Male
Middle Aged
Mitotane
Quality of Life
Streptozocin
Young Adult

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1056/NEJMoa1200966

Steroid Profiling as a Biomarker Tool in the Diagnosis and Monitoring of Adrenal Tumours
Arlt, W. (Principal Investigator) & Stewart, P. (Co-Investigator)
Medical Research Council
2/03/09 → 29/02/12
Project: Research Councils

Cite this

Fassnacht, M., Terzolo, M., Allolio, B., Baudin, E., Haak, H., Berruti, A., Welin, S., Schade-Brittinger, C., Lacroix, A., Jarzab, B., Sorbye, H., Torpy, D. J., Stepan, V., Schteingart, D. E., Arlt, W., Kroiss, M., Leboulleux, S., Sperone, P., Sundin, A., ... FIRM-ACT Study Group (2012). Combination chemotherapy in advanced adrenocortical carcinoma. The New England Journal of Medicine, 366(23), 2189-97. https://doi.org/10.1056/NEJMoa1200966

@article{0217704c58f04a0391ecd0d49a8f4401,

title = "Combination chemotherapy in advanced adrenocortical carcinoma",

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.).",

keywords = "Adrenal Cortex Neoplasms, Adrenocortical Carcinoma, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Cisplatin, Disease-Free Survival, Doxorubicin, Etoposide, Female, Humans, Intention to Treat Analysis, Kaplan-Meier Estimate, Male, Middle Aged, Mitotane, Quality of Life, Streptozocin, Young Adult",

author = "Martin Fassnacht and Massimo Terzolo and Bruno Allolio and Eric Baudin and Harm Haak and Alfredo Berruti and Staffan Welin and Carmen Schade-Brittinger and Andr{\'e} Lacroix and Barbara Jarzab and Halfdan Sorbye and Torpy, {David J} and Vinzenz Stepan and Schteingart, {David E} and Wiebke Arlt and Matthias Kroiss and Sophie Leboulleux and Paola Sperone and Anders Sundin and Ilse Hermsen and Stefanie Hahner and Willenberg, {Holger S} and Antoine Tabarin and Marcus Quinkler and {de la Fouchardi{\`e}re}, Christelle and Martin Schlumberger and Franco Mantero and Dirk Weismann and Felix Beuschlein and Hans Gelderblom and Hanneke Wilmink and Monica Sender and Maureen Edgerly and Werner Kenn and Tito Fojo and Hans-Helge M{\"u}ller and Britt Skogseid and {FIRM-ACT Study Group}",

year = "2012",

month = jun,

day = "7",

doi = "10.1056/NEJMoa1200966",

language = "English",

volume = "366",

pages = "2189--97",

journal = "The New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachusetts Medical Society",

number = "23",

}

Fassnacht, M, Terzolo, M, Allolio, B, Baudin, E, Haak, H, Berruti, A, Welin, S, Schade-Brittinger, C, Lacroix, A, Jarzab, B, Sorbye, H, Torpy, DJ, Stepan, V, Schteingart, DE, Arlt, W, Kroiss, M, Leboulleux, S, Sperone, P, Sundin, A, Hermsen, I, Hahner, S, Willenberg, HS, Tabarin, A, Quinkler, M, de la Fouchardière, C, Schlumberger, M, Mantero, F, Weismann, D, Beuschlein, F, Gelderblom, H, Wilmink, H, Sender, M, Edgerly, M, Kenn, W, Fojo, T, Müller, H-H, Skogseid, B & FIRM-ACT Study Group 2012, 'Combination chemotherapy in advanced adrenocortical carcinoma', The New England Journal of Medicine, vol. 366, no. 23, pp. 2189-97. https://doi.org/10.1056/NEJMoa1200966

TY - JOUR

T1 - Combination chemotherapy in advanced adrenocortical carcinoma

AU - Fassnacht, Martin

AU - Terzolo, Massimo

AU - Allolio, Bruno

AU - Baudin, Eric

AU - Haak, Harm

AU - Berruti, Alfredo

AU - Welin, Staffan

AU - Schade-Brittinger, Carmen

AU - Lacroix, André

AU - Jarzab, Barbara

AU - Sorbye, Halfdan

AU - Torpy, David J

AU - Stepan, Vinzenz

AU - Schteingart, David E

AU - Arlt, Wiebke

AU - Kroiss, Matthias

AU - Leboulleux, Sophie

AU - Sperone, Paola

AU - Sundin, Anders

AU - Hermsen, Ilse

AU - Hahner, Stefanie

AU - Willenberg, Holger S

AU - Tabarin, Antoine

AU - Quinkler, Marcus

AU - de la Fouchardière, Christelle

AU - Schlumberger, Martin

AU - Mantero, Franco

AU - Weismann, Dirk

AU - Beuschlein, Felix

AU - Gelderblom, Hans

AU - Wilmink, Hanneke

AU - Sender, Monica

AU - Edgerly, Maureen

AU - Kenn, Werner

AU - Fojo, Tito

AU - Müller, Hans-Helge

AU - Skogseid, Britt

AU - FIRM-ACT Study Group

PY - 2012/6/7

Y1 - 2012/6/7

N2 - 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.).

AB - 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.).

KW - Adrenal Cortex Neoplasms

KW - Adrenocortical Carcinoma

KW - Adult

KW - Aged

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Cisplatin

KW - Disease-Free Survival

KW - Doxorubicin

KW - Etoposide

KW - Female

KW - Humans

KW - Intention to Treat Analysis

KW - Kaplan-Meier Estimate

KW - Male

KW - Middle Aged

KW - Mitotane

KW - Quality of Life

KW - Streptozocin

KW - Young Adult

U2 - 10.1056/NEJMoa1200966

DO - 10.1056/NEJMoa1200966

M3 - Article

C2 - 22551107

SN - 0028-4793

VL - 366

SP - 2189

EP - 2197

JO - The New England Journal of Medicine

JF - The New England Journal of Medicine

IS - 23

ER -

Combination chemotherapy in advanced adrenocortical carcinoma

Abstract

Keywords

UN SDGs

Access to Document

Fingerprint

Projects

Steroid Profiling as a Biomarker Tool in the Diagnosis and Monitoring of Adrenal Tumours

Cite this