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 tre atment of advanced breast cancer (ABC). This study evaluated the combinatio n 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 175 mg/m(2) intravenous (IV) by a 3-hour infusion on day 1, while mitoxantrone was given by 2 mg/m(2) increments, starting from 10 mg/m (2) by bolus IV injection on day 1 after paclitaxel. Cycles were repeated e very 3 weeks. Mitoxantrone doses were increased if the maximum tolerated do se (MTD) had not been reached. Result: The overall response rate (CR + PR) was 69% (CI 95%: 55-83). Six (1 4%) 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 survi val were 7 months (range 1-26) and 12 months (range 2-29), respectively. Af ter 12 months 14 (33%) patients had died and 8 (19%) patients were alive af ter 18 months. MTD was reached at 14 mg/m(2) level of mitoxantrone. Leukope nia was evident in 39 (93%) of total patients and was severe in 28 (67%) pa tients. All non-hematological toxicity observed was mild. Conclusion: This trial shows the activity of paclitaxel and mitoxantrone in ABC and finds that a dose of 14 mg/m(2) of mitoxantrone is the MTD in comb ination with a fixed dose of 175 mg/m(2) of paclitaxel without granulocyte colony stimulating factor (G-CSF).