Phase I/II trial of high dose mitoxantrone in metastatic breast cancer: The M.D. Anderson Cancer Center experience

Massimo Cristofanilli, Frankie Ann Holmes, Laura Esparza, Vicente Valero, Aman U. Buzdar, James A. Neidhart, Gabriel N. Hortobagyi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Anthracyclines are among the most active agents in metastatic breast cancer. Mitoxantrone demonstrated a different toxicity profile when compared to doxorubicin. We performed a phase I/II study of single-agent high-dose mitoxantrone therapy for advanced breast cancer. Nineteen patients who had a diagnosis of metastatic breast cancer received treatment at the M.D. Anderson Cancer Center between June 1986 and December 1987. The patients received escalating doses of mitoxantrone until a maximum tolerated dose (MTD), defined as grade 3 or 4 nonhematologic toxicity or infection, was obtained. The starting dose of 25 mg/m2, given by short intravenous infusion, was escalated by 25% in each five-patient cohort if each patient in the previous cohort tolerated the initial course and 2 or fewer patients reached the MTD. The median cumulative dose of mitoxantrone was 93 mg/m2 (range, 25-205) and the maximum single dose was 39 mg/m2. Myelosuppression was the dose limiting toxicity. The median duration of granulocyte count ≤ 250/μl was 5-7 days. Four patients (22%) had infections that required hospitalization, 3 patients (17%) had cardiac toxicity. One patient (6%) achieved a complete response, and 3 (17%) had a partial response, with an overall response rate of 22.3%. No apparent dose-response relationship was observed in our study. The mitoxantrone dosage recommended for phase II studies is 25 mg/m2 every 3-4 weeks. We conclude that high-dose mitoxantrone therapy for metastatic breast cancer was relatively well tolerated but was not associated with a higher response rate than that of standard dose mitoxantrone.

Original languageEnglish (US)
Pages (from-to)225-233
Number of pages9
JournalBreast Cancer Research and Treatment
Issue number3
StatePublished - 1999


  • Cardiac toxicity
  • Dose intensity
  • Metastatic breast cancer
  • Mitoxantrone
  • Myelosuppression
  • Single agent chemotherapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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