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

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Abstract

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.

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Authors and Affiliations

  1. Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

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

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  1. Massimo Cristofanilli
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  2. Frankie Ann Holmes
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  3. Laura Esparza
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  4. Vicente Valero
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  5. Aman U. Buzdar
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  6. James A. Neidhart
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  7. Gabriel N. Hortobagyi
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Cristofanilli, M., Holmes, F.A., Esparza, L. et al. Phase I/II trial of high dose mitoxantrone in metastatic breast cancer: the M.D. Anderson Cancer Center experience. Breast Cancer Res Treat 54, 225–233 (1999). https://doi.org/10.1023/A:1006104610727

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