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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

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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.

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Acknowledgements

We thank all of the patients who participated in this trial and all of the research staff at study centers who helped to recruit patients and provide data. This work was partly supported by a Grant-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare of Japan.

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Authors and Affiliations

  1. Department of Pediatrics, Mie University Graduate School of Medicine, Tsu, Japan

    Hiroki Hori & Yoshihiro Komada

  2. Department of Pediatrics, Hokkaido Medical Center for Child Health and Rehabilitation, Sapporo, Japan

    Tooru Kudoh

  3. Department of Pediatrics, Hiroshima University Graduate School of Biomedical Science, Hiroshima, Japan

    Shinichiro Nishimura

  4. Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    Megumi Oda

  5. Department of Pediatrics, Asahikawa Medical College, Asahikawa, Japan

    Makoto Yoshida

  6. Department of Pediatrics, Osaka City General Hospital, Osaka, Japan

    Junichi Hara

  7. Department of Pediatrics, Osaka Medical Center, Osaka, Japan

    Akio Tawa

  8. Department of Pediatrics, Kobe City Medical Center General Hospital, Kobe, Japan

    Ikuya Usami

  9. Department of Pediatrics, University of Fukui Faculty of Medical Science, Fukui, Japan

    Akihiko Tanizawa

  10. Department of Pediatrics, Osaka General Medical Center, Osaka, Japan

    Keiko Yumura-Yagi

  11. Department of Hematology and Oncology, Children’s Medical Center, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

    Koji Kato

  12. Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan

    Ryoji Kobayashi

  13. Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan

    Keitaro Matsuo

  14. Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan

    Hiroki Hori & Keizo Horibe

  15. Department of Medical Education, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan

    Hiroki Hori

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  1. Hiroki Hori
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  2. Tooru Kudoh
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  7. Akio Tawa
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  10. Keiko Yumura-Yagi
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  15. Keizo Horibe
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For the Japan Association of Childhood Leukemia Study

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Correspondence to Hiroki Hori.

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The authors declare that they have no conflict of interest.

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Hori, H., Kudoh, T., Nishimura, S. et al. 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. Int J Clin Oncol 22, 387–396 (2017). https://doi.org/10.1007/s10147-016-1062-1

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  • DOI: https://doi.org/10.1007/s10147-016-1062-1

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