Docetaxel-ifosfamide combination in patients with advanced breast cancer failing prior anthracycline-based regimens: results of a phase I-II study.

The established clinical activity of docetaxel and ifosfamide as single agents in anthracycline pre-treated breast cancer, led us to conduct a phase I-II study to define the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and clinical activity of the docetaxel+ifosfamide combination in this setting. Patients with histologically confirmed metastatic breast cancer, after failure on prior anthracycline-based chemotherapy, were treated at successive dose levels (DLs) in cohorts of 3-6 with escalated doses of docetaxel 70-100 mg/m(2) over 1 h on day 1 followed by ifosfamide 5-6 g/m(2) divided over days 1+2 (2.5-3.0 g/m(2)/day over 1 h), every 21 days. G-CSF was added once dose-limiting neutropenia was encountered at a certain DL and planned to be incorporated prophylactically in subsequent higher DLs. Between March 1997 and December 2002, 65 patients with a median age of 57 years (range, 32-72) and performance status (WHO) of 1 (range, 0-2) were treated at 5 DLs as follows; 21 in phase I DLs (DL1: 3, DL2: 6, DL3: 3, DL4: 6, and DL5: 3) and the remaining 44 were treated at DL4 (total of 50 patients at DL4), which was defined as the level for phase II testing. All patients were assessable for toxicity and 62 for response. DLT (with the addition of G-CSF after DL2) was reached at DL5 with 2/3 initial patients developing febrile neutropenia. Clinical response rates (RRs), on an intention-to-treat basis, in phase II were: 56%; (95% CI, 42.2-69.7%); 4 CRs, 24 PRs, 10 SD and 12 PD. The median response duration was 7 mo (3-24 mo), median TTP 6.5 mo (0.1-26 mo), and median OS 13 mo (0.1-33 mo). Grade 3/4 toxicities included: neutropenia in 72% of patients, with 60% developing grade 4 neutropenia (

Dose escalation of docetaxel and ifosfamide in patients with advanced breast cancer failing prior anthracyclines: mature results of a phase I-II study.

PURPOSE: Single-agent docetaxel and ifosfamide are clinically active in anthracycline-pretreated advanced breast cancer. We conducted a phase I-II study aiming to define the maximum tolerated dose (MTD), the dose-limiting toxicities (DLTs), and the activity of the docetaxel-ifosfamide combination in this setting. PATIENTS AND METHODS: Cohorts of 3-6 patients with histologically confirmed metastatic breast cancer after prior anthracycline-based chemotherapy were treated at successive dose levels (DLs) with escalated doses of docetaxel (70-100 mg/m(2) over 1 h on day 1), followed by ifosfamide 5-6 g/m(2) divided over days 1 and 2 (2.5-3.0 g/m(2)/day over 1 h), and recycled every 21 days. G-CSF was added once dose-limiting neutropenia was encountered at a certain DL and planned to be incorporated prophylactically in subsequent higher DLs. RESULTS: Sixty-five patients (median age 57 years, range 32-72) and performance status (PS) (World Health Organization-WHO) of 1 (range 0-2) were treated at 5 DLs as follows: 21 in phase I DLs (DL1: 3, DL2: 6, DL3: 3, DL4: 6, and DL5: 3) and the remaining 44 were treated at DL4 (total of 50 patients at DL4), which was defined as the level for phase II testing. All patients were evaluable for toxicity and 62 for response. DLT (with the addition of G-CSF after DL2) was reached at DL5 with 2/3 initial patients developing febrile neutropenia. Clinical response rates (RRs), on an intention-to-treat basis, in phase II were 56% (95% CI 42.2-69.7): complete remission (CR) 4, partial remission (PR) 24, stable disease (SD) 10 and progressive disease (PD) 12. The median response duration was 7 months (range 3-24), the median time to progression (TTP) 6.5 months (range 0.1-26), and the median overall survival (OS) 13 months (range 0.1-33). Grade 3/4 toxicities included neutropenia in 72% of patients-with 60% developing grade 4 neutropenia (