Phase I/II trial of high dose mitoxantrone in metastatic breast cancer: the M.D. Anderson Cancer Center experience.
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.
Cristofanilli
M
M
Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Holmes
F A
FA
Esparza
L
L
Valero
V
V
Buzdar
A U
AU
Neidhart
J A
JA
Hortobagyi
G N
GN
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
D008942:Mitoxantrone