Dose intensification of mitoxantrone in combination with paclitaxel in advanced breast cancer: a phase II study

Background: Paclitaxel and mitoxantrone are highly active agents in the treatment of advanced breast cancer (ABC). This study evaluated the combination of paclitaxel and mitoxantrone in patients with advanced breast cancer to determine activity and toxicity.Patients and method: 42 patients with ABC were treated with paclitaxel at a fixed dose of 175mg/m2 intravenous (IV) by a 3hour infusion on day 1, while mitoxantrone was given by 2mg/m2 increments, starting from 10mg/m2 by bolus IV injection on day 1 after paclitaxel. Cycles were repeated every 3 weeks. Mitoxantrone doses were increased if the maximum tolerated dose (MTD) had not been reached.Result: The overall response rate (CR + PR) was 69% (CI 95%: 55–83). Six (14%) patients obtained CR and 23 (55%) PR with a median duration of response of 8 months (range 2–16). There were no differences in response rates (RR) between the three levels of mitoxantrone. Median time to failure and survival were 7 months (range 1–26) and 12 months (range 2–29), respectively. After 12 months 14 (33%) patients had died and 8 (19%) patients were alive after 18 months. MTD was reached at 14mg/m2 level of mitoxantrone. Leukopenia was evident in 39 (93%) of total patients and was severe in 28 (67%) patients. All nonhematological toxicity observed was mild.Conclusion: This trial shows the activity of paclitaxel and mitoxantrone in ABC and finds that a dose of 14mg/m2 of mitoxantrone is the MTD in combination with a fixed dose of 175mg/m2 of paclitaxel without granulocyte colony stimulating factor (GCSF).