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Anthracyclines and anthracenedionesIn useRational design

Mitoxantrone

Also known as Novantrone

A synthetic anthracenedione given by injection. Its 2012 US label lists multiple sclerosis, pain related to advanced hormone-refractory prostate cancer, and initial therapy of acute nonlymphocytic leukaemia in adults.

From discovery to approval

  1. 1978 · Earliest report found

    A 1978 Journal of Medicinal Chemistry paper by Zee-Cheng and Cheng reported 1,4-dihydroxy-5,8-bis[[2-(hydroxyethyl)amino]ethyl]amino-9,10-anthracenedione (DHAQ), highly active against mouse P-388 leukaemia and B-16 melanoma. The US label gives this chemical name for mitoxantrone, and a 1980 paper titles it mitoxantrone (NSC 301739).[2][3][4][5][6][1]

  2. 1987-12-23 · FDA regular

    The letter of 23 December 1987 states that adequate information was presented to demonstrate that the product is safe and effective for use as initial therapy for acute nonlymphocytic leukaemia in adults, with labeling revisions. The letter is a scanned image read by OCR. The type regular is an inference: no accelerated-approval wording was found.[7]

How it works

The label describes a DNA-reactive agent that intercalates into DNA through hydrogen bonding, causing crosslinks and strand breaks. It also interferes with RNA and is a potent inhibitor of topoisomerase II, and it kills both proliferating and nonproliferating cultured human cells.[1]

Where it came from and why

A 1989 review states that mitoxantrone was synthesised to try to develop a doxorubicin-like drug with a better therapeutic index. A 1979 paper by Murdock and colleagues on a related anthracenedione series describes a 5,8-dihydroxy compound with 2-hydroxyethyl groups that equalled or surpassed adriamycin and daunorubicin in P388 efficacy and therapeutic index; its abstract does not name mitoxantrone.

Cancers

  • Acute nonlymphocytic leukaemia

    The 2012 US label lists mitoxantrone with other approved drugs for initial therapy of acute nonlymphocytic leukaemia in adults; the 1987 FDA approval letter states initial therapy for this disease as the approved use.[1]

  • Prostate cancer, hormone-refractory

    In a Canadian randomised trial of 161 patients with pain, a palliative response occurred in 29% given mitoxantrone plus prednisone and 12% given prednisone alone, with no difference in overall survival.[8]

  • Relapsed childhood acute lymphoblastic leukaemia

    In the ALL R3 trial, children with first relapse were randomised to idarubicin or mitoxantrone in induction and the trial stopped randomisation because of differences in progression-free and overall survival.[9]

  • Breast cancer, non-Hodgkin lymphoma and ovarian cancer

    A 1989 review lists clinical activity in acute leukaemias, breast carcinoma, non-Hodgkin lymphoma and ovarian cancer.[6]

Worth knowing

  • The label also lists mitoxantrone for reducing neurologic disability or relapse frequency in secondary progressive, progressive relapsing or worsening relapsing-remitting multiple sclerosis, and not for primary progressive multiple sclerosis.[1]
  • In a placebo-controlled trial of 194 patients with multiple sclerosis, mitoxantrone 12 mg/m2 every 3 months for 24 months improved the primary multivariate outcome (difference 0.30, 95% CI 0.17 to 0.44; p<0.0001).[10]
  • The label states that cancer patients who received cumulative doses of 140 mg/m2, alone or with other chemotherapy, had a 2.6% cumulative probability of clinical congestive heart failure.[1]
  • In a trial of 1006 men with metastatic hormone-refractory prostate cancer, median survival was 16.5 months with mitoxantrone plus prednisone and 18.9 months with docetaxel every 3 weeks plus prednisone (hazard ratio for death 0.76, 95% CI 0.62 to 0.94).[11]
  • A 1979 mouse study of CL 232315 (NSC 301739D), whose chemical name matches mitoxantrone's, reported that, unlike Adriamycin, it was active against intravenously implanted L1210 leukaemia and had moderate activity against an Adriamycin-resistant P388 subline.[4]

On this site

References

  1. U.S. Food and Drug Administration. Novantrone (mitoxantrone hydrochloride) concentrate for injection: prescribing information (NDA 019297 supplement 035, 23 March 2012). Source
  2. Zee-Cheng RK, Cheng CC. Antineoplastic agents. Structure-activity relationship study of bis(substituted aminoalkylamino)anthraquinones. J Med Chem. 1978;21(3):291-4. PubMedDOI
  3. Murdock KC, Child RG, Fabio PF, Angier RB, Wallace RE, Durr FE, et al. Antitumor agents. 1. 1,4-Bis[(aminoalkyl)amino]-9,10-anthracenediones. J Med Chem. 1979;22(9):1024-30. PubMedDOI
  4. Wallace RE, Murdock KC, Angier RB, Durr FE. Activity of a novel anthracenedione, 1,4-dihydroxy-5,8-bis(((2-[(2-hydroxyethyl)amino]ethyl)amino])-9,10-anthracenedione dihydrochloride, against experimental tumors in mice. Cancer Res. 1979;39(5):1570-4. PubMed
  5. Hagenberg L, Loynds P, Nagel GA. [Mitoxantrone HCl (1,4-dihydroxy-4, 8-bis[[2-(hydroxyethyl)-amino-ethyl)]amino 9,10-anthracenedione dihydrochloride (NSC 301739) - a new cytostatic]. Onkologie. 1980;3(6):322-8. PubMed
  6. Weiss RB. Mitoxantrone: its development and role in clinical practice. Oncology (Williston Park). 1989;3(6):135-41; discussion 141-3, 147-8. PubMed
  7. U.S. Food and Drug Administration. Novantrone (mitoxantrone hydrochloride concentrate for injection), NDA 19-297: original approval package including the approval letter of 23 December 1987 (scanned document, read by OCR). Source
  8. Tannock IF, Osoba D, Stockler MR, Ernst DS, Neville AJ, Moore MJ, et al. Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points. J Clin Oncol. 1996;14(6):1756-64. PubMedDOI
  9. Parker C, Waters R, Leighton C, Hancock J, Sutton R, Moorman AV, et al. Effect of mitoxantrone on outcome of children with first relapse of acute lymphoblastic leukaemia (ALL R3): an open-label randomised trial. Lancet. 2010;376(9757):2009-17. PubMedDOI
  10. Hartung HP, Gonsette R, König N, Kwiecinski H, Guseo A, Morrissey SP, et al. Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial. Lancet. 2002;360(9350):2018-25. PubMedDOI
  11. Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351(15):1502-12. PubMedDOI
  12. U.S. Food and Drug Administration. Drugs@FDA: Approval date(s) and history, letters, labels, reviews for NDA 019297 (Novantrone, mitoxantrone hydrochloride). Page read 2026-10-29. Source
  13. Hospira, Inc. Mitoxantrone injection, solution, concentrate: prescribing information. DailyMed, set ID accf9569-4b57-4e83-a7db-4e890a75d1ba, published 17 July 2025. Source