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, Michaela Haaf, Sarah Johanssen, Ann-Cathrin Koschker, Katharina Laubner, Silviu Sbiera, Jürgen Schiemann, Sebastian Wortmann, Matthias Haase, Matthias Schott, Matthias Möhlig, Kathrin Zopf, Nicole Reisch, Matthias Betz, Martin Reincke, Behrend Isermann, Stefan Bornstein, Christian Fottner, Anna Böse, Stephan Petersenn, Holger Leitolf, Silke Klose, Hans Wolf, Cecile Chougnet, Julie More, Marie Laure Nunes, Jean Pierre Droz, Patricia Nicolli, Olivier Chabre, Annie Clergeot, Franck Schillo, Alfred Penfornis, Christine Do Cao, Francois Goldwasser, Patrice Rodien, Anna Ferrero, Paola Perotti, Maria Verena Cicala, Patalano Anna, Silvia della Casa, Massimo Mannelli, Valentina Piccini, M Wouter Dercksen, J A Hans Romijn, Jan Ouwerkerk, J Hans DeVries, Barbro Eriksson, Eva Tiensuu Janson, Dan Granberg, Kjell Öberg, Håkan Ahlman, Mikael Garkavij, Naime Wall, Ursula Falkmer, Gary Hammer, Harold J Olney, Isabelle Bourdeau, Lucienne Bourque, Sylwia Szpak-Ulczok, Michal Jarzab, Harald Holte, Alexander Fosså, Ferdinand Ploner, Ulrich Mansmann, Hans-Joachim Schmoll, Bengt Simonsson, Vincenzo Toscano, 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, Michaela Haaf, Sarah Johanssen, Ann-Cathrin Koschker, Katharina Laubner, Silviu Sbiera, Jürgen Schiemann, Sebastian Wortmann, Matthias Haase, Matthias Schott, Matthias Möhlig, Kathrin Zopf, Nicole Reisch, Matthias Betz, Martin Reincke, Behrend Isermann, Stefan Bornstein, Christian Fottner, Anna Böse, Stephan Petersenn, Holger Leitolf, Silke Klose, Hans Wolf, Cecile Chougnet, Julie More, Marie Laure Nunes, Jean Pierre Droz, Patricia Nicolli, Olivier Chabre, Annie Clergeot, Franck Schillo, Alfred Penfornis, Christine Do Cao, Francois Goldwasser, Patrice Rodien, Anna Ferrero, Paola Perotti, Maria Verena Cicala, Patalano Anna, Silvia della Casa, Massimo Mannelli, Valentina Piccini, M Wouter Dercksen, J A Hans Romijn, Jan Ouwerkerk, J Hans DeVries, Barbro Eriksson, Eva Tiensuu Janson, Dan Granberg, Kjell Öberg, Håkan Ahlman, Mikael Garkavij, Naime Wall, Ursula Falkmer, Gary Hammer, Harold J Olney, Isabelle Bourdeau, Lucienne Bourque, Sylwia Szpak-Ulczok, Michal Jarzab, Harald Holte, Alexander Fosså, Ferdinand Ploner, Ulrich Mansmann, Hans-Joachim Schmoll, Bengt Simonsson, Vincenzo Toscano
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.).
Source: PubMed