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Cancer Chemotherapy and Pharmacology

, Volume 5, Issue 1, pp 11–15 | Cite as

Phase I clinical trial of mitoxantrone: A new anthracenedione anticancer drug

  • David S. Alberts
  • Katherine S. Griffith
  • Gary E. Goodman
  • Terence S. Herman
  • Edward Murray
Original Articles Mitoxantrone Clinical Trial

Summary

Mitoxantrone, 1,4-dihydroxy-5,8-bis(((2-[(2-hydroxyethyl)amino]ethyl) amino))-9,10-anthra-cenedione dihydrochloride, a new antitumor agent was evaluated in nine cancer patients as part of a phase I trial. In general, the drug was well tolerated. Leukopenia was the dose-limiting toxic effect. Mild to moderate leukopenia (but not neutropenia or thrombocytopenia) occurred in four of six patients given 4 mg/m2/week after a mean of 2.75 doses (range, 2–4 doses) and in all three patients given 5 mg/m2/week after three doses. Only one patient had mild nausea and vomiting. No patient experienced alopecia or mucositis, and none showed evidence of any cardiac, renal, hepatic, or pulmonary abnormality. Mitoxantrone treatment induced two partial remissions (patients with metastatic squamous cell carcinomas of the hypopharynx and rectum) and one mixed response (patient with gastric carcinoma). For phase II studies the starting dose, when used on a weekly schedule, should be 5 mg/m2 in patients who are known to have adequate bone marrow reserve.

Keywords

Squamous Cell Carcinoma Neutropenia Alopecia Mitoxantrone Partial Remission 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Wallace RE, Murdock KC, Angier RB, Durr FE (1979) 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 39:1570Google Scholar
  2. 2.
    Murdock KC, Child RG, Nabir PF, Angier RB, Wallace RE, Durr FE, Citarella RV (1979) Antitumor agents I. 1,4-bis[(aminoalkyl)amino]-9,10-anthracenediones. J Med Chem 22:1024Google Scholar
  3. 3.
    Zee-Cheng RKY, Cheng CC (1978) Antineoplastic agents. Structure activity relationship study of bis (substituted aminoalkylamino) anthraquinones. J Med Chem 21:291Google Scholar
  4. 4.
    Johnson RK, Zee-Cheng RKY, Lee WW, Acton FM, Henry DW, Cheng CC (1979) Experimental antitumor activity of aminoanthraquinones. Cancer Treat Rep 63:425Google Scholar
  5. 5.
    Cheng CC, Zbinden G, Zee-Cheng RKY (1979) Comparison of antineoplastic activity of aminoethylaminoanthraquinones and anthracycline antibiotics. J Pharm Sci 68:383Google Scholar
  6. 6.
    Von Hoff DD, Pollard E, Kuhn J, Murray E, Coltman CA Jr (1980) Phase I clinical investigation of 1,4-dihydroxy-5,8-bis(((2-[(2-hydroxyethyl)amino]-ethyl)amino))-9,10-anthracenedione dihydrochloride (NSC 301739), a new anthracenedione. Cancer Res 40:1516Google Scholar

Copyright information

© Springer-Verlag 1980

Authors and Affiliations

  • David S. Alberts
    • 1
    • 2
  • Katherine S. Griffith
    • 1
    • 2
  • Gary E. Goodman
    • 1
    • 2
  • Terence S. Herman
    • 3
  • Edward Murray
    • 4
  1. 1.Section of Hematology/Oncology, Department of Medicine College of MedicineUniversity of ArizonaTucson
  2. 2.the Cancer Center, College of MedicineUniversity of ArizonaTucson
  3. 3.Section of Hematology/Oncology, Department of MedicineVeterans Administration HospitalTucson
  4. 4.Medical Research DivisionAmerican Cyanamid Co., Lederle LaboratoriesPearl RiverUSA

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