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 d oxorubicin. We performed a phase I/II study of single-agent high-dose mitox antrone therapy for advanced breast cancer. Nineteen patients who had a dia gnosis of metastatic breast cancer received treatment at the M.D. Anderson Cancer Center between June 1986 and December 1987. The patients received es calating doses of mitoxantrone until a maximum tolerated dose (MTD), define d as grade 3 or 4 nonhematologic toxicity or infection, was obtained. The s tarting dose of 25 mg/m(2,) given by short intravenous infusion, was escala ted by 25% in each five-patient cohort if each patient in the previous coho rt tolerated the initial course and 2 or fewer patients reached the MTD. Th e median cumulative dose of mitoxantrone was 93 mg/m(2) (range, 25-205) and the maximum single dose was 39 mg/m(2). Myelosuppression was the dose limi ting toxicity. The median duration of granulocyte count less than or equal to 250/mu l was 5-7 days. Four patients (22%) had infections that required hospitalization, 3 patients (17%) had cardiac toxicity. One patient (6%) ac hieved a complete response, and 3 (17%) had a partial response, with an ove rall response rate of 22.3%. No apparent dose-response relationship was obs erved in our study. The mitoxantrone dosage recommended for phase II studie s is 25 mg/m(2) every 3-4 weeks. We conclude that high-dose mitoxantrone th erapy for metastatic breast cancer was relatively well tolerated but was no t associated with a higher response rate than that of standard dose mitoxan trone.