Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study
Johannes Lammer, Katarina Malagari, Thomas Vogl, Frank Pilleul, Alban Denys, Anthony Watkinson, Michael Pitton, Geraldine Sergent, Thomas Pfammatter, Sylvain Terraz, Yves Benhamou, Yves Avajon, Thomas Gruenberger, Maria Pomoni, Herbert Langenberger, Marcus Schuchmann, Jerome Dumortier, Christian Mueller, Patrick Chevallier, Riccardo Lencioni, PRECISION V Investigators, Johannes Lammer, Herbert Langenberger, Maria Schoder, Martin Funovics, Christian Loewe, Johanna Moyses, Thomas Grünberger, Christian Müller, Peter Waldenberger, Andreas Chemelli, Ivo Graziadei, Thomas Vogl, Verena Khan, Renate Hammerstingl, Clara Lee, Kathrin Eichler, Michael Pitton, Roman Klöckner, Christoph Düber, Gerd Otto, Marcus-Alexander Wörns, Tim Greten, Timm Kirchhoff, Herbert Rosenthal, Joachim Lotz, Peter Huppert, Hubertus Wietholtz, A Limmer, Frank Pilleul, Sabine Ficarelli, Nicolas Mennesson, Nathalie Rauscher, Jerome Dumortier, Olivier Guillaud, Valerie Vilgrain, Annie Sibert, Patrick Chevallier, Sebastien Novellas, Albert Tran, Denis Ouzan, Jean Gugenheim, Géraldine Sergent, Pillippe Otal, Francis Joffre, Julien Auriol, Jean Marie Péron, Yves Benhamou, Vlad Ratzui, Phillipe Clluzel, Thierry de Baere, Frederic Deschamps, Pramod Roo, Yves Ajavon, Sameh Awad, Marie-France Bellin, Didier Samuel, Denis Castaing, Rene Adam, Jean-Charles Duclos Vallee, Faouzy Saliba, Daniel Azoulay, Alban Denys, Juergen Triller, Ralph Kickuth, Sylvain Terraz, Christoph D Becker, Pietro Majno, Laurent Spahr, Thomas Pfammatter, Dominik Weishaupt, Beat Muellhaupt, Katerina Malagari, Pomoni Maria, Dimitrios Kelekis, Nikolaos Kelekis, Alexis Kelekis, Emmanouil Emmanouil, Johannes Lammer, Katarina Malagari, Thomas Vogl, Frank Pilleul, Alban Denys, Anthony Watkinson, Michael Pitton, Geraldine Sergent, Thomas Pfammatter, Sylvain Terraz, Yves Benhamou, Yves Avajon, Thomas Gruenberger, Maria Pomoni, Herbert Langenberger, Marcus Schuchmann, Jerome Dumortier, Christian Mueller, Patrick Chevallier, Riccardo Lencioni, PRECISION V Investigators, Johannes Lammer, Herbert Langenberger, Maria Schoder, Martin Funovics, Christian Loewe, Johanna Moyses, Thomas Grünberger, Christian Müller, Peter Waldenberger, Andreas Chemelli, Ivo Graziadei, Thomas Vogl, Verena Khan, Renate Hammerstingl, Clara Lee, Kathrin Eichler, Michael Pitton, Roman Klöckner, Christoph Düber, Gerd Otto, Marcus-Alexander Wörns, Tim Greten, Timm Kirchhoff, Herbert Rosenthal, Joachim Lotz, Peter Huppert, Hubertus Wietholtz, A Limmer, Frank Pilleul, Sabine Ficarelli, Nicolas Mennesson, Nathalie Rauscher, Jerome Dumortier, Olivier Guillaud, Valerie Vilgrain, Annie Sibert, Patrick Chevallier, Sebastien Novellas, Albert Tran, Denis Ouzan, Jean Gugenheim, Géraldine Sergent, Pillippe Otal, Francis Joffre, Julien Auriol, Jean Marie Péron, Yves Benhamou, Vlad Ratzui, Phillipe Clluzel, Thierry de Baere, Frederic Deschamps, Pramod Roo, Yves Ajavon, Sameh Awad, Marie-France Bellin, Didier Samuel, Denis Castaing, Rene Adam, Jean-Charles Duclos Vallee, Faouzy Saliba, Daniel Azoulay, Alban Denys, Juergen Triller, Ralph Kickuth, Sylvain Terraz, Christoph D Becker, Pietro Majno, Laurent Spahr, Thomas Pfammatter, Dominik Weishaupt, Beat Muellhaupt, Katerina Malagari, Pomoni Maria, Dimitrios Kelekis, Nikolaos Kelekis, Alexis Kelekis, Emmanouil Emmanouil
Abstract
Transcatheter arterial chemoembolization (TACE) offers a survival benefit to patients with intermediate hepatocellular carcinoma (HCC). A widely accepted TACE regimen includes administration of doxorubicin-oil emulsion followed by gelatine sponge-conventional TACE. Recently, a drug-eluting bead (DC Bead) has been developed to enhance tumor drug delivery and reduce systemic availability. This randomized trial compares conventional TACE (cTACE) with TACE with DC Bead for the treatment of cirrhotic patients with HCC. Two hundred twelve patients with Child-Pugh A/B cirrhosis and large and/or multinodular, unresectable, N0, M0 HCCs were randomized to receive TACE with DC Bead loaded with doxorubicin or cTACE with doxorubicin. Randomization was stratified according to Child-Pugh status (A/B), performance status (ECOG 0/1), bilobar disease (yes/no), and prior curative treatment (yes/no). The primary endpoint was tumor response (EASL) at 6 months following independent, blinded review of MRI studies. The drug-eluting bead group showed higher rates of complete response, objective response, and disease control compared with the cTACE group (27% vs. 22%, 52% vs. 44%, and 63% vs. 52%, respectively). The hypothesis of superiority was not met (one-sided P = 0.11). However, patients with Child-Pugh B, ECOG 1, bilobar disease, and recurrent disease showed a significant increase in objective response (P = 0.038) compared to cTACE. DC Bead was associated with improved tolerability, with a significant reduction in serious liver toxicity (P < 0.001) and a significantly lower rate of doxorubicin-related side effects (P = 0.0001). TACE with DC Bead and doxorubicin is safe and effective in the treatment of HCC and offers a benefit to patients with more advanced disease.
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