Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2005 Jul-Sep;10(3):337-46.

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

Affiliations
  • PMID: 17357187

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

C Cosmas et al. J BUON. 2005 Jul-Sep.

Abstract

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 (</= 7 days) and 10% of these febrile neutropenia (FN), while no grade 3/4 thrombocytopenia was observed. Other toxicities included grade 2 peripheral neuropathy only in 10% of the patients, grade 1/2 reversible CNS toxicity in 16%, no renal toxicity, grade 2 myalgias in 8%, grade 3 diarrhea in 8%, skin/nail toxicity in 14%, and grade 2 fluid retention in 2%. One patient treated at the phase II part of the study died of acute liver failure after the first cycle.

Conclusion: The present phase I-II study determined the feasibility, defined the MTD and demonstrated the encouraging activity of the docetaxel-ifosfamide combination in the phase II part of the study. Therefore, future randomized phase III studies versus single-agent docetaxel or combinations of the latter with other active agents are warranted.

PubMed Disclaimer

LinkOut - more resources