title: Acute and late toxicities of pirarubicin in the treatment of childhood acute lymphoblastic leukemia: results from a clinical trial by the Japan Association of Childhood Leukemia Study.
abstract: BACKGROUND
  Anthracyclines are used to treat childhood acute lymphoblastic leukemia (ALL). Even when administered at low doses, these agents are reported to cause progressive cardiac dysfunction. We conducted a clinical trial comparing the toxicities of two anthracyclines, pirarubicin (THP) and daunorubicin (DNR), in the treatment of childhood ALL. The results from our study that relate to acute and late toxicities are reported here.
  
  
  METHODS
  276 children with B-ALL were enrolled in the trial from April 1997 to March 2002 and were randomly assigned to receive a regimen including either THP (25 mg/m2× 11) or DNR (30 mg/m2× 11). Acute toxicity was prospectively assessed based on the National Cancer Institute Common Toxicity Criteria. Acute hematological toxicity was also examined via some parameters. Patients with event-free survival of >5 years were retrospectively surveyed for cardiac function at 5 and 10 years and at the most recent assessment more than 10 years from the onset of ALL.
  
  
  RESULTS
  Acute hematological toxicity in the early phase was more significant in the THP arm. Based on ultrasound cardiography, cardiac function was impaired in both groups during the follow-up period, but there was no significant difference between the groups except for a greater decline in fractional shortening on ultrasound cardiography in the DNR arm.
  
  
  CONCLUSIONS
  While acute hematological toxicity was more significant in the THP arm, THP also appeared to be less cardiotoxic. However, the evaluation of late cardiotoxicity was limited because only a few subjects were followed beyond 10 years after ALL onset. Considering that the THP regimen produced an EFS rate comparable with that of the DNR regimen, the efficacy and toxicity of THP at reduced doses should be studied in order to identify potentially safer regimens.
authors.affiliation: Department of Pediatrics, Mie University Graduate School of Medicine, Tsu, Japan. hhori@clin.medic.mie-u.ac.jp.|Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan. hhori@clin.medic.mie-u.ac.jp.|Department of Medical Education, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan. hhori@clin.medic.mie-u.ac.jp.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Hori
authors.affiliation: Department of Pediatrics, Hokkaido Medical Center for Child Health and Rehabilitation, Sapporo, Japan.
authors.forename: Tooru
authors.initials: T
authors.lastname: Kudoh
authors.affiliation: Department of Pediatrics, Hiroshima University Graduate School of Biomedical Science, Hiroshima, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Nishimura
authors.affiliation: Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Oda
authors.affiliation: Department of Pediatrics, Asahikawa Medical College, Asahikawa, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Department of Pediatrics, Osaka City General Hospital, Osaka, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Hara
authors.affiliation: Department of Pediatrics, Osaka Medical Center, Osaka, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Tawa
authors.affiliation: Department of Pediatrics, Kobe City Medical Center General Hospital, Kobe, Japan.
authors.forename: Ikuya
authors.initials: I
authors.lastname: Usami
authors.affiliation: Department of Pediatrics, University of Fukui Faculty of Medical Science, Fukui, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Tanizawa
authors.affiliation: Department of Pediatrics, Osaka General Medical Center, Osaka, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Yumura-Yagi
authors.affiliation: Department of Hematology and Oncology, Children's Medical Center, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Kato
authors.affiliation: Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Kobayashi
authors.affiliation: Department of Pediatrics, Mie University Graduate School of Medicine, Tsu, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Komada
authors.affiliation: Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.affiliation: Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
authors.forename: Keizo
authors.initials: K
authors.lastname: Horibe
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D000208:Acute Disease; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D003630:Daunorubicin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D006331:Heart Diseases / Q000139:chemically induced / Q000453:epidemiology; D007564:Japan / Q000453:epidemiology; D009367:Neoplasm Staging; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies
chemical_list: D018943:Anthracyclines; D003630:Daunorubicin; D004317:Doxorubicin; C027260:pirarubicin
keywords: Cardiotoxicity; Childhood leukemia; Clinical trial; Long-term follow-up; Myelotoxicity; Pirarubicin