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Pre-administration of docetaxel protects against adriamycin-induced cardiotoxicity

  • Preclinical Study
  • Published:
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Abstract

Background

We have revealed in a pre-clinical study that the combination of adriamycin (ADR) and docetaxel (DOC) in which ADR was administered 12 h after DOC injection not only significantly reduced leukopenia and toxic death but also significantly increased the antitumor effect compared with the dosing schedule without an interval between each injection used commonly in clinical practice. The purpose of this study was to clarify in mice whether the toxic death caused by ADR was reduced by administering ADR after DOC injection when the doses and dosing-interval of ADR and DOC were changed.

Methods

ADR alone or a combination of ADR and DOC (ADR/DOC group in which both drugs were administered simultaneously or DOC-ADR group in which ADR was administered after DOC injection) was administered every 7 days in mice.

Results

When dosing intervals (0–24 h) were changed, there were no differences in survival rate among the 6, 12, and 24-h interval groups, although these groups showed significantly higher survival rate compared with the ADR/DOC group. When the dose of ADR (2.5–15 mg/kg) was changed, the survival rate was higher in all the DOC-ADR groups than the ADR alone groups. When the dose of DOC (3.125–12.5 mg/kg) was changed, DOC caused a dose-dependent reduction in toxic death. Although there was no striking difference in adverse effects between the ADR alone and DOC-ADR groups, the DOC-ADR group showed markedly attenuated increases in CPK-MB activity compared with the ADR alone group.

Conclusions

We conclude that pre-administration of DOC may protect against ADR-induced toxic death and cardiotoxicity.

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Abbreviations

ADR:

Adriamycin

DOC:

Docetaxel

MBC:

Metastatic breast cancer

CPK-MB:

Creatine phosphokinase-isoenzyme-MB

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Acknowledgments

We are indebted to Kyowa Hakko Kogyo Co. Ltd. for supplying the ADR used in this study. This study was supported by a Grant-in-Aid for Scientific Research on Priority Areas (H. T., 18014021) from the Ministry of Education, Culture, Sports, Science and Technology, Japan. This project was partially supported by a Grant-in-aid for Scientific Research from Nagasaki University, Japan (H. T.) and the research Foundation for Pharmaceutical Sciences (H. T.).

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Authors and Affiliations

  1. Clinical Pharmacokinetics, Division of Clinical Pharmacy, Department of Medico-Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Hiromi Sakaguchi, Ayumi Kodama, Yukie Ando, Mayumi Tabuchi & Shun Higuchi

  2. Department of Hospital Pharmacy, Nagasaki University Hospital of Medicine and Dentistry, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan

    Mari Tomonari, Hideto To, Ryosuke Araki, Takashi Kitahara & Hitoshi Sasaki

  3. Clinical Pharmaceutics, Division of Clinical Pharmacy, Department of Medico-Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Shigehiro Ohdo

Authors
  1. Hiromi Sakaguchi
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  2. Ayumi Kodama
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  3. Mari Tomonari
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  4. Yukie Ando
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  5. Mayumi Tabuchi
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  6. Hideto To
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  7. Ryosuke Araki
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  8. Takashi Kitahara
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  9. Hitoshi Sasaki
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  10. Shigehiro Ohdo
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  11. Shun Higuchi
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Corresponding author

Correspondence to Hideto To.

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Sakaguchi, H., Kodama, A., Tomonari, M. et al. Pre-administration of docetaxel protects against adriamycin-induced cardiotoxicity. Breast Cancer Res Treat 109, 443–450 (2008). https://doi.org/10.1007/s10549-007-9667-8

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  • DOI: https://doi.org/10.1007/s10549-007-9667-8

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