Retinoic acid and arsenic trioxide for acute promyelocytic leukemia

F. Lo-Coco, G. Avvisati, M. Vignetti, C. Thiede, S. M. Orlando, S. Iacobelli, F. Ferrara, P. Fazi, L. Cicconi, E. Di Bona, G. Specchia, S. Sica, M. Divona, A. Levis, W. Fiedler, E. Cerqui, M. Breccia, G. Fioritoni, H. R. Salih, M. CazzolaL. Melillo, A. M. Carella, C. H. Brandts, E. Morra, M. Von Lilienfeld-Toal, B. Hertenstein, M. Wattad, M. Lübbert, M. Hänel, N. Schmitz, H. Link, M. G. Kropp, A. Rambaldi, G. La Nasa, M. Luppi, F. Ciceri, O. Finizio, A. Venditti, F. Fabbiano, K. Döhner, M. Sauer, A. Ganser, S. Amadori, F. Mandelli, H. Döhner, G. Ehninger, R. F. Schlenk, U. Platzbecker

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Abstract

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, ≤10×109per 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

Original languageEnglish
Pages (from-to)111-121
Number of pages11
JournalNew England Journal of Medicine
Volume369
Issue number2
DOIs
Publication statusPublished - 2013

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Acute Promyelocytic Leukemia
Tretinoin
Drug Therapy
Disease-Free Survival
arsenic trioxide
Idarubicin
Therapeutics
Standard of Care
Multicenter Studies
Survival Rate
Cell Count

ASJC Scopus subject areas

  • Medicine(all)

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Lo-Coco, F., Avvisati, G., Vignetti, M., Thiede, C., Orlando, S. M., Iacobelli, S., ... Platzbecker, U. (2013). Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. New England Journal of Medicine, 369(2), 111-121. https://doi.org/10.1056/NEJMoa1300874

Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. / Lo-Coco, F.; Avvisati, G.; Vignetti, M.; Thiede, C.; Orlando, S. M.; Iacobelli, S.; Ferrara, F.; Fazi, P.; Cicconi, L.; Di Bona, E.; Specchia, G.; Sica, S.; Divona, M.; Levis, A.; Fiedler, W.; Cerqui, E.; Breccia, M.; Fioritoni, G.; Salih, H. R.; Cazzola, M.; Melillo, L.; Carella, A. M.; Brandts, C. H.; Morra, E.; Von Lilienfeld-Toal, M.; Hertenstein, B.; Wattad, M.; Lübbert, M.; Hänel, M.; Schmitz, N.; Link, H.; Kropp, M. G.; Rambaldi, A.; La Nasa, G.; Luppi, M.; Ciceri, F.; Finizio, O.; Venditti, A.; Fabbiano, F.; Döhner, K.; Sauer, M.; Ganser, A.; Amadori, S.; Mandelli, F.; Döhner, H.; Ehninger, G.; Schlenk, R. F.; Platzbecker, U.

In: New England Journal of Medicine, Vol. 369, No. 2, 2013, p. 111-121.

Research output: Contribution to journalArticle

Lo-Coco, F, Avvisati, G, Vignetti, M, Thiede, C, Orlando, SM, Iacobelli, S, Ferrara, F, Fazi, P, Cicconi, L, Di Bona, E, Specchia, G, Sica, S, Divona, M, Levis, A, Fiedler, W, Cerqui, E, Breccia, M, Fioritoni, G, Salih, HR, Cazzola, M, Melillo, L, Carella, AM, Brandts, CH, Morra, E, Von Lilienfeld-Toal, M, Hertenstein, B, Wattad, M, Lübbert, M, Hänel, M, Schmitz, N, Link, H, Kropp, MG, Rambaldi, A, La Nasa, G, Luppi, M, Ciceri, F, Finizio, O, Venditti, A, Fabbiano, F, Döhner, K, Sauer, M, Ganser, A, Amadori, S, Mandelli, F, Döhner, H, Ehninger, G, Schlenk, RF & Platzbecker, U 2013, 'Retinoic acid and arsenic trioxide for acute promyelocytic leukemia', New England Journal of Medicine, vol. 369, no. 2, pp. 111-121. https://doi.org/10.1056/NEJMoa1300874
Lo-Coco, F. ; Avvisati, G. ; Vignetti, M. ; Thiede, C. ; Orlando, S. M. ; Iacobelli, S. ; Ferrara, F. ; Fazi, P. ; Cicconi, L. ; Di Bona, E. ; Specchia, G. ; Sica, S. ; Divona, M. ; Levis, A. ; Fiedler, W. ; Cerqui, E. ; Breccia, M. ; Fioritoni, G. ; Salih, H. R. ; Cazzola, M. ; Melillo, L. ; Carella, A. M. ; Brandts, C. H. ; Morra, E. ; Von Lilienfeld-Toal, M. ; Hertenstein, B. ; Wattad, M. ; Lübbert, M. ; Hänel, M. ; Schmitz, N. ; Link, H. ; Kropp, M. G. ; Rambaldi, A. ; La Nasa, G. ; Luppi, M. ; Ciceri, F. ; Finizio, O. ; Venditti, A. ; Fabbiano, F. ; Döhner, K. ; Sauer, M. ; Ganser, A. ; Amadori, S. ; Mandelli, F. ; Döhner, H. ; Ehninger, G. ; Schlenk, R. F. ; Platzbecker, U. / Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. In: New England Journal of Medicine. 2013 ; Vol. 369, No. 2. pp. 111-121.
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title = "Retinoic acid and arsenic trioxide for acute promyelocytic leukemia",
abstract = "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, ≤10×109per 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",
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T1 - Retinoic acid and arsenic trioxide for acute promyelocytic leukemia

AU - Lo-Coco, F.

AU - Avvisati, G.

AU - Vignetti, M.

AU - Thiede, C.

AU - Orlando, S. M.

AU - Iacobelli, S.

AU - Ferrara, F.

AU - Fazi, P.

AU - Cicconi, L.

AU - Di Bona, E.

AU - Specchia, G.

AU - Sica, S.

AU - Divona, M.

AU - Levis, A.

AU - Fiedler, W.

AU - Cerqui, E.

AU - Breccia, M.

AU - Fioritoni, G.

AU - Salih, H. R.

AU - Cazzola, M.

AU - Melillo, L.

AU - Carella, A. M.

AU - Brandts, C. H.

AU - Morra, E.

AU - Von Lilienfeld-Toal, M.

AU - Hertenstein, B.

AU - Wattad, M.

AU - Lübbert, M.

AU - Hänel, M.

AU - Schmitz, N.

AU - Link, H.

AU - Kropp, M. G.

AU - Rambaldi, A.

AU - La Nasa, G.

AU - Luppi, M.

AU - Ciceri, F.

AU - Finizio, O.

AU - Venditti, A.

AU - Fabbiano, F.

AU - Döhner, K.

AU - Sauer, M.

AU - Ganser, A.

AU - Amadori, S.

AU - Mandelli, F.

AU - Döhner, H.

AU - Ehninger, G.

AU - Schlenk, R. F.

AU - Platzbecker, U.

PY - 2013

Y1 - 2013

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, ≤10×109per 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

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, ≤10×109per 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

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