title: Phase I/II trial of high dose mitoxantrone in metastatic breast cancer: the M.D. Anderson Cancer Center experience.
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 < or = 250/microl 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.
authors.affiliation: Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
authors.forename: M
authors.initials: M
authors.lastname: Cristofanilli
authors.forename: F A
authors.initials: FA
authors.lastname: Holmes
authors.forename: L
authors.initials: L
authors.lastname: Esparza
authors.forename: V
authors.initials: V
authors.lastname: Valero
authors.forename: A U
authors.initials: AU
authors.lastname: Buzdar
authors.forename: J A
authors.initials: JA
authors.lastname: Neidhart
authors.forename: G N
authors.initials: GN
authors.lastname: Hortobagyi
mesh_terms: D000328:Adult; D000465:Algorithms; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage* / Q000009:adverse effects*; D009362:Neoplasm Metastasis / Q000188:drug therapy
chemical_list: D008942:Mitoxantrone