Hiroki Hori1,2,3, Tooru Kudoh4, Shinichiro Nishimura5, Megumi Oda6, Makoto Yoshida7, Junichi Hara8, Akio Tawa9, Ikuya Usami10, Akihiko Tanizawa11, Keiko Yumura-Yagi12, Koji Kato13, Ryoji Kobayashi14, Yoshihiro Komada15, Keitaro Matsuo16, Keizo Horibe17. 1. Department of Pediatrics, Mie University Graduate School of Medicine, Tsu, Japan. hhori@clin.medic.mie-u.ac.jp. 2. Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan. hhori@clin.medic.mie-u.ac.jp. 3. 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. 4. Department of Pediatrics, Hokkaido Medical Center for Child Health and Rehabilitation, Sapporo, Japan. 5. Department of Pediatrics, Hiroshima University Graduate School of Biomedical Science, Hiroshima, Japan. 6. Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. 7. Department of Pediatrics, Asahikawa Medical College, Asahikawa, Japan. 8. Department of Pediatrics, Osaka City General Hospital, Osaka, Japan. 9. Department of Pediatrics, Osaka Medical Center, Osaka, Japan. 10. Department of Pediatrics, Kobe City Medical Center General Hospital, Kobe, Japan. 11. Department of Pediatrics, University of Fukui Faculty of Medical Science, Fukui, Japan. 12. Department of Pediatrics, Osaka General Medical Center, Osaka, Japan. 13. Department of Hematology and Oncology, Children's Medical Center, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan. 14. Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan. 15. Department of Pediatrics, Mie University Graduate School of Medicine, Tsu, Japan. 16. Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan. 17. Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
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.
RCT Entities:
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.
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