Retinoic acid and arsenic trioxide for acute promyelocytic leukemia
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Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. / Lo-Coco, Francesco; Avvisati, Giuseppe; Vignetti, Marco; Thiede, Christian; Orlando, Sonia Maria; Iacobelli, Simona; Ferrara, Felicetto; Fazi, Paola; Cicconi, Laura; Di Bona, Eros; Specchia, Giorgina; Sica, Simona; Divona, Mariadomenica; Levis, Alessandro; Fiedler, Walter; Cerqui, Elisa; Breccia, Massimo; Fioritoni, Giuseppe; Salih, Helmut R; Cazzola, Mario; Melillo, Lorella; Carella, Angelo M; Brandts, Christian H; Morra, Enrica; von Lilienfeld-Toal, Marie; Hertenstein, Bernd; Wattad, Mohammed; Lübbert, Michael; Hänel, Matthias; Schmitz, Norbert; Link, Hartmut; Kropp, Maria Grazia; Rambaldi, Alessandro; La Nasa, Giorgio; Luppi, Mario; Ciceri, Fabio; Finizio, Olimpia; Venditti, Adriano; Fabbiano, Francesco; Döhner, Konstanze; Sauer, Michaela; Ganser, Arnold; Amadori, Sergio; Mandelli, Franco; Döhner, Hartmut; Ehninger, Gerhard; Schlenk, Richard F; Platzbecker, Uwe; Gruppo Italiano Malattie Ematologiche dell'Adulto.
In: NEW ENGL J MED, Vol. 369, No. 2, 11.07.2013, p. 111-21.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Retinoic acid and arsenic trioxide for acute promyelocytic leukemia
AU - Lo-Coco, Francesco
AU - Avvisati, Giuseppe
AU - Vignetti, Marco
AU - Thiede, Christian
AU - Orlando, Sonia Maria
AU - Iacobelli, Simona
AU - Ferrara, Felicetto
AU - Fazi, Paola
AU - Cicconi, Laura
AU - Di Bona, Eros
AU - Specchia, Giorgina
AU - Sica, Simona
AU - Divona, Mariadomenica
AU - Levis, Alessandro
AU - Fiedler, Walter
AU - Cerqui, Elisa
AU - Breccia, Massimo
AU - Fioritoni, Giuseppe
AU - Salih, Helmut R
AU - Cazzola, Mario
AU - Melillo, Lorella
AU - Carella, Angelo M
AU - Brandts, Christian H
AU - Morra, Enrica
AU - von Lilienfeld-Toal, Marie
AU - Hertenstein, Bernd
AU - Wattad, Mohammed
AU - Lübbert, Michael
AU - Hänel, Matthias
AU - Schmitz, Norbert
AU - Link, Hartmut
AU - Kropp, Maria Grazia
AU - Rambaldi, Alessandro
AU - La Nasa, Giorgio
AU - Luppi, Mario
AU - Ciceri, Fabio
AU - Finizio, Olimpia
AU - Venditti, Adriano
AU - Fabbiano, Francesco
AU - Döhner, Konstanze
AU - Sauer, Michaela
AU - Ganser, Arnold
AU - Amadori, Sergio
AU - Mandelli, Franco
AU - Döhner, Hartmut
AU - Ehninger, Gerhard
AU - Schlenk, Richard F
AU - Platzbecker, Uwe
AU - Gruppo Italiano Malattie Ematologiche dell'Adulto
PY - 2013/7/11
Y1 - 2013/7/11
N2 - BACKGROUND: All-trans retinoic acid (ATRA) with chemotherapy is the standard of care for acute promyelocytic leukemia (APL), resulting in cure rates exceeding 80%. Pilot studies of treatment with arsenic trioxide with or without ATRA have shown high efficacy and reduced hematologic toxicity.METHODS: We conducted a phase 3, multicenter trial comparing ATRA plus chemotherapy with ATRA plus arsenic trioxide in patients with APL classified as low-to-intermediate risk (white-cell count, ≤10×10(9) per liter). Patients were randomly assigned to receive either ATRA plus arsenic trioxide for induction and consolidation therapy or standard ATRA-idarubicin induction therapy followed by three cycles of consolidation therapy with ATRA plus chemotherapy and maintenance therapy with low-dose chemotherapy and ATRA. The study was designed as a noninferiority trial to show that the difference between the rates of event-free survival at 2 years in the two groups was not greater than 5%.RESULTS: Complete remission was achieved in all 77 patients in the ATRA-arsenic trioxide group who could be evaluated (100%) and in 75 of 79 patients in the ATRA-chemotherapy group (95%) (P=0.12). The median follow-up was 34.4 months. Two-year event-free survival rates were 97% in the ATRA-arsenic trioxide group and 86% in the ATRA-chemotherapy group (95% confidence interval for the difference, 2 to 22 percentage points; P<0.001 for noninferiority and P=0.02 for superiority of ATRA-arsenic trioxide). Overall survival was also better with ATRA-arsenic trioxide (P=0.02). As compared with ATRA-chemotherapy, ATRA-arsenic trioxide was associated with less hematologic toxicity and fewer infections but with more hepatic toxicity.CONCLUSIONS: ATRA plus arsenic trioxide is at least not inferior and may be superior to ATRA plus chemotherapy in the treatment of patients with low-to-intermediate-risk APL. (Funded by Associazione Italiana contro le Leucemie and others; ClinicalTrials.gov number, NCT00482833.).
AB - BACKGROUND: All-trans retinoic acid (ATRA) with chemotherapy is the standard of care for acute promyelocytic leukemia (APL), resulting in cure rates exceeding 80%. Pilot studies of treatment with arsenic trioxide with or without ATRA have shown high efficacy and reduced hematologic toxicity.METHODS: We conducted a phase 3, multicenter trial comparing ATRA plus chemotherapy with ATRA plus arsenic trioxide in patients with APL classified as low-to-intermediate risk (white-cell count, ≤10×10(9) per liter). Patients were randomly assigned to receive either ATRA plus arsenic trioxide for induction and consolidation therapy or standard ATRA-idarubicin induction therapy followed by three cycles of consolidation therapy with ATRA plus chemotherapy and maintenance therapy with low-dose chemotherapy and ATRA. The study was designed as a noninferiority trial to show that the difference between the rates of event-free survival at 2 years in the two groups was not greater than 5%.RESULTS: Complete remission was achieved in all 77 patients in the ATRA-arsenic trioxide group who could be evaluated (100%) and in 75 of 79 patients in the ATRA-chemotherapy group (95%) (P=0.12). The median follow-up was 34.4 months. Two-year event-free survival rates were 97% in the ATRA-arsenic trioxide group and 86% in the ATRA-chemotherapy group (95% confidence interval for the difference, 2 to 22 percentage points; P<0.001 for noninferiority and P=0.02 for superiority of ATRA-arsenic trioxide). Overall survival was also better with ATRA-arsenic trioxide (P=0.02). As compared with ATRA-chemotherapy, ATRA-arsenic trioxide was associated with less hematologic toxicity and fewer infections but with more hepatic toxicity.CONCLUSIONS: ATRA plus arsenic trioxide is at least not inferior and may be superior to ATRA plus chemotherapy in the treatment of patients with low-to-intermediate-risk APL. (Funded by Associazione Italiana contro le Leucemie and others; ClinicalTrials.gov number, NCT00482833.).
KW - Adult
KW - Aged
KW - Antineoplastic Combined Chemotherapy Protocols
KW - Arsenicals
KW - Consolidation Chemotherapy
KW - Disease-Free Survival
KW - Female
KW - Humans
KW - Induction Chemotherapy
KW - Leukemia, Promyelocytic, Acute
KW - Maintenance Chemotherapy
KW - Male
KW - Middle Aged
KW - Neutropenia
KW - Oxides
KW - Thrombocytopenia
KW - Tretinoin
KW - Young Adult
U2 - 10.1056/NEJMoa1300874
DO - 10.1056/NEJMoa1300874
M3 - SCORING: Journal article
C2 - 23841729
VL - 369
SP - 111
EP - 121
JO - NEW ENGL J MED
JF - NEW ENGL J MED
SN - 0028-4793
IS - 2
ER -