ANTHRACYCLINES - A REVIEW OF GENERAL AND SPECIAL TOXICITY STUDIES

  • Authors:
    • G MAZUE
    • M IATROPOULOS
    • A IMONDI
    • S CASTELLINO
    • M BRUGHERA
    • A PODESTA
    • P DELLATORRE
    • D MONETA
  • View Affiliations

  • Published online on: October 1, 1995     https://doi.org/10.3892/ijo.7.4.713
  • Pages: 713-726
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Abstract

Preclinical safety assessment data on doxorubicin (DOXO), epirubicin (EPI), idarubicin (IDA) and methoxymorpholinodoxorubicin (MORPHO), from mouse, rat and dog studies are reviewed. These data are put into perspective allowing for extrapolations across species, doses and dose regimens with recommendations for proper human use. The compounds were administered intravenously or intraperitoneally in studies ranging from single dose to multiple dose studies of different durations. The compounds were given once, daily, weekly or cyclically. In the cyclic administration studies, DOXO, EPI, and IDA were given for 3 consecutive days a week for 6 or 13 weeks; MORPHO was given for 3 consecutive days a week every three weeks for a total of 9 cycles. The duration of the cyclic studies was from 6-26 weeks. Daily dose studies lasted from 4-26 weeks. In the single dose studies the recovery ranged from 4 weeks to one year; in the multiple dose studies from 4 to 8 weeks. A few special studies were also considered. In all studies reviewed, 2 different types of toxicity were observed. These toxicities occur also in man. The first is the acute toxicity, which is the consequence of cytotoxicity and expresses the exaggerated pharmacological activity of the compounds. The target sites in all 3 species and in man include the hemolymphopoietic system (HLPS), the gastrointestinal (GI) tract, skin and testes; all renewing cell types. The second type of toxicity is the chronic progressive toxicity. This toxicity is the expression and result of sustained disruption of cytoplasmic homeostasis and occurs in non-renewing cell types. The target sites include the heart (both animals and man), kidneys (rodents) and peripheral nervous system (PNS) (rodents). From single administration animal data, chronicity, site and magnitude of toxicities can be predicted in man. Despite strong mitogenic stimuli in the rat, there is no evidence that there is a potential for hemolympho- or hepatocarcinogenicity with these compounds.

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October 1995
Volume 7 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
MAZUE G, IATROPOULOS M, IMONDI A, CASTELLINO S, BRUGHERA M, PODESTA A, DELLATORRE P and MONETA D: ANTHRACYCLINES - A REVIEW OF GENERAL AND SPECIAL TOXICITY STUDIES. Int J Oncol 7: 713-726, 1995
APA
MAZUE, G., IATROPOULOS, M., IMONDI, A., CASTELLINO, S., BRUGHERA, M., PODESTA, A. ... MONETA, D. (1995). ANTHRACYCLINES - A REVIEW OF GENERAL AND SPECIAL TOXICITY STUDIES. International Journal of Oncology, 7, 713-726. https://doi.org/10.3892/ijo.7.4.713
MLA
MAZUE, G., IATROPOULOS, M., IMONDI, A., CASTELLINO, S., BRUGHERA, M., PODESTA, A., DELLATORRE, P., MONETA, D."ANTHRACYCLINES - A REVIEW OF GENERAL AND SPECIAL TOXICITY STUDIES". International Journal of Oncology 7.4 (1995): 713-726.
Chicago
MAZUE, G., IATROPOULOS, M., IMONDI, A., CASTELLINO, S., BRUGHERA, M., PODESTA, A., DELLATORRE, P., MONETA, D."ANTHRACYCLINES - A REVIEW OF GENERAL AND SPECIAL TOXICITY STUDIES". International Journal of Oncology 7, no. 4 (1995): 713-726. https://doi.org/10.3892/ijo.7.4.713