Paclitaxel combined with ifosfamide in anthracycline-and docetaxel-pretreated metastatic breast cancer: Activity independence of prior docetaxel resistance

Background: We evaluated the efficacy and tolerability of combined paclitaxel and ifosfamide in anthracycline-and docetaxel-pretreated metastatic breast cancer (MBC). Methods:Patients received paclitaxel (175 mg/m² i.v. in a 3-h infusion) on day 1 and ifosfamide (1.5 g/m² i.v. in a 15-min infusion) on days 1-3, every 3 weeks for a maximum of nine cycles. The tumor response was assessed every two cycles. Results: We enrolled 34 patients with a median age of 50 years. Thirty patients had visceral metastases. Anthracycline-and docetaxel-based chemotherapy had previously been administered to 18/13 and 13/21 patients, respectively, in (neo)adjuvant/metastatic settings. Three patients had not previously received anthracycline due to abnormal cardiac functions. A total of 174 cycles of chemotherapy were delivered with a median of six cycles. The response rate under the intent-to-treat analysis was 23.5% (all partial responses) with a median response duration of 14 months. The disease control rate was 70.6%. The median progression-free and overall survival were 5.9 and 8.5 months, respectively. There was no apparent relationship between activity and prior docetaxel resistance. The incidence of grade III/IV neutropenia was 46.6% (81 of 174 cycles) with febrile neutropenia of only 1.7%. Major grade III/IV nonhematological toxicities included peripheral neuropathy (6 of 34 patients) and infection (4 of 34 patients). There were no treatment-related deaths. Conclusion:Paclitaxel combined with ifosfamide was effective and tolerable in anthracycline-/docetaxel-pretreated MBC. Overcoming docetaxel resistance by using paclitaxel in combination with ifosfamide needs to be addressed through further investigation.