title: Tamibarotene in patients with acute promyelocytic leukaemia relapsing after treatment with all-trans retinoic acid and arsenic trioxide.
abstract: Treatment of acute promyelocytic leukaemia (APL) with arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) is highly effective first-line therapy, although approximately 5-10% of patients relapse. Tamibarotene is a synthetic retinoid with activity in APL patients who relapse after chemotherapy and ATRA, but has not been studied in relapse after treatment with ATO and ATRA. We report on a phase II study of tamibarotene in adult patients with relapsed or refractory APL after treatment with ATRA and ATO (n = 14). Participants were treated with tamibarotene (6 mg/m(2) /d) during induction and for up to six cycles of consolidation. The overall response rate was 64% (n = 9), the rate of complete cytogenetic response was 43% (n = 6) and the rate of complete molecular response was 21% (n = 3). Relapse was frequent with 7 of 9 responders relapsing after a median of 4·6 months (range 1·6-26·8 months). The median event-free survival (EFS) was 3·5 months [95% confidence interval (CI) 0-8·6 months] and the median overall survival (OS) was 9·5 months (95% CI 5·9-13·1 months). These results demonstrate that tamibarotene has activity in relapsed APL after treatment with ATO and ATRA and further studies using tamibarotene as initial therapy and in combination with ATO are warranted.
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: David
authors.initials: D
authors.lastname: Sanford
authors.affiliation: Department of Biomedicine and Prevention, University Tor Vergata of Rome, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Lo-Coco
authors.affiliation: Hematology Department, Hospital Universitario La Fe, Valencia, Spain.|Department of Medicine, University of Valencia, Valencia, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Sanz
authors.affiliation: Hematology Unit, San Bortolo Hospital, Vicenza, Italy.
authors.forename: Eros
authors.initials: E
authors.lastname: Di Bona
authors.affiliation: Stanford Cancer Center, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Coutre
authors.affiliation: Robert H. Lurie Comprehensive Cancer Center, Northwestern University School of Medicine, Chicago, IL, USA.
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Altman
authors.affiliation: Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Meir
authors.initials: M
authors.lastname: Wetzler
authors.affiliation: Department of Medicine, Hofstra North Shore-Long Island Jewish School of Medicine, Hempstead, NY, USA.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Allen
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Cortes
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage / Q000627:therapeutic use; D001565:Benzoates / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D002318:Cardiovascular Diseases / Q000139:chemically induced; D002454:Cell Differentiation / Q000187:drug effects; D003131:Combined Modality Therapy; D060830:Consolidation Chemotherapy; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D064147:Febrile Neutropenia / Q000139:chemically induced; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D053208:Kaplan-Meier Estimate; D015473:Leukemia, Promyelocytic, Acute / Q000097:blood / Q000188:drug therapy* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000097:blood; D010087:Oxides / Q000008:administration & dosage / Q000627:therapeutic use; D012008:Recurrence; D012074:Remission Induction; D016879:Salvage Therapy; D013764:Tetrahydronaphthalenes / Q000009:adverse effects / Q000627:therapeutic use*; D014212:Tretinoin / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D001565:Benzoates; D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; D010087:Oxides; D013764:Tetrahydronaphthalenes; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; C061133:tamibarotene; D014212:Tretinoin; D000077237:Arsenic Trioxide
keywords: Acute promyelocytic leukaemia; all-trans retinoic acid; arsenic trioxide; clinical trial; tamibarotene