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Cancer in Pregnancy: Mitoxantrone

Mitoxantrone (Novantrone) is 1,4-dihydroxy-5,8-bis ((2-((2-hydroxyethyl)amino)ethyl)amino)anthraquinone, often abbreviated DHAQ. It is an antineoplastic agent that appears to bind DNA and produce strand scission 1,2.

Setting Treatment Outcomes
In vitro studies mammalian assay systems Mitoxantrone is genotoxic in several mammalian assay systems 3-5.
Species studied
Animal studies * Rabbits up to 0.4 mg/kg/day We have been unable to locate references on possible developmental toxicity of mitoxantrone; however, ametantrone, a similar agent, was teratogenic in rabbits at doses of 0.4mg/kg/day but not at 0.2 mg/kg/day 6.
Rats up to 6 mg/kg/day Ametantrone was not teratogenic in rats at up to 6 mg/kg/day 6.
Study design
Human studies Case reports 2nd trimester Combination with: cytarabine + idarubicin Two case reports have described the use of mitroxantrone during the second trimester of human pregnancy 7,8. In one case, five weeks of therapy with mitroxantrone and cytarabine up to developmental week 28 were accompanied by normal fetal growth 7. Subsequent introduction of idarubicin to replace mitroxantrone was followed by death of the fetus. In the second case, a mother treated with a variety of chemotherapeutic agents including mitroxantrone from 24 to 34 weeks of gestation delivered a normal female infant 8.
Breast feeding Pharmacokinetic Mitoxantrone is excreted in breast milk in small amounts 8.
Case reports Based on data from one lactating mother, this agent is apparently stored and released slowly into breast milk for at least one month after its administration 8. Although the quantities of drug in milk were very low (10-20 ng/mL), breastfeeding was not recommended in this case.
* - None of the animal studies reported in this table were conducted at The Hospital for Sick Children, Toronto, or by Motherisk.

References

  1. Alberts DS et al: Pharmacology of mitoxantrone: mode of action and pharmacokinetics. Invest New Drugs 3:101-7, 1985.
  2. Locher SE, Meyn RE: Relationship between cytotoxicity and DNA damage in mammalian cells treated with anthracenedione derivatives. Chem Biol Interact 46:369-79, 1983.
  3. Manandhar M et al: Genetic toxicology profile of the new antineoplastic drug mitoxantrone in the mammalian test systems. Arzneimittelforschung 36:1375-9, 1986.
  4. Au WW et al: Comparative structure-genotoxicity study of three aminoathraquinone drugs and doxorubicin. Cancer Res 41:376-9, 1981.
  5. Rosenberg LJ, Hittelman WN: Direct and indirect clastogenic activity of anthracenedione in Chinese hamster ovary cells. Cancer Res 43:3270-5,1983.
  6. Petrere JA et al: Teratology studies of ametantrone acetate in rats and rabbits. Teratology 34:271-8, 1986.
  7. Reynoso EE, Huerta F: Acute leukemia and pregnancy - fatal fetal outcome after exposure to idarubicin during the second trimester. ActaOncologica 33:703-16, 1994.
  8. Azuno Y, Kaku K, Fujita N: Mitoxantrone and etoposide in breast milk. Am J Hematol 48:131-2, 1995.
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The information on this website is not intended as a substitute for the advice and care of your doctor or other health-care provider. Always consult your doctor if you have any questions about exposures during pregnancy and before you take any medications.

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