Investigational New Drugs

, Volume 25, Issue 5, pp 463–470 | Cite as

Docetaxel–ifosfamide combination in patients with HER2-non-overexpressing advanced breast cancer failing prior anthracyclines

  • Christos Kosmas
  • Nicolas Tsavaris
  • Nikolaos Malamos
  • George Tsakonas
  • Argyris Gassiamis
  • Aristidis Polyzos
  • Nicolas Mylonakis
  • Athanasios Karabelis
PHASE II STUDIES
First Online:
Received:
Accepted:

Summary

The feasibility of the docetaxel–ifosfamide combination, as well as the definition of maximum tolerated doses (MTD) in a previous phase I study, led us to continue evaluating the regimen in an extended phase II study in patients with HER2-non-overexpressing, anthracycline pre-treated advanced breast cancer. Patients with histologically confirmed metastatic breast cancer failing prior anthracycline-based chemotherapy were treated with docetaxel 100 mg/m2 over 1 h on day 1 followed by ifosfamide 5 g/m2 divided over days 1 and 2 (2.5 g/m2/day over 1 h), and recycled every 21 days with prophylactic granulocyte-colony stimulating factor (G-CSF) administration from day 3—until a neutrophil count >10,000/μl. Between March 1999 and June 2002, 71 patients with a median age of 55 years (range, 28–72) and performance status (World Health Organization; WHO) of 1 (range, 0–2) were treated; all were assessable for toxicity and 70 patients for response. Clinical response rates (RRs), on an intention-to-treat basis were: 41/71 [58%; 95% CI, 46.5–69.5%]; 7 complete remissions (CRs), 34 partial remissions (PRs), 15 stable disease (SD) and 15 progressive disease (PD). The median response duration was 7.5 months (2–28 months), median time-to-progression (TTP) 6 months (0.1–30 months), and median overall survival (OS) 12 months (0.1–36 months). Grade 3/4 toxicities included; neutropenia in 63% of patients—with 52% developing grade 4 neutropenia (≥7 days) and in 11% of these febrile neutropenia (FN), while no grade 3/4 thrombocytopenia was observed. Other toxicities included; peripheral neuropathy grade 2 only in 7%, grade 1/2 reversible central nervous system (CNS) toxicity in 11%, no renal toxicity, grade 2 myalgias in 7%, grade 3 diarrhea in 4%, skin/nail toxicity in 11%, and grade 1/2 fluid retention in 28% of patients. The present report has demonstrated encouraging activity of the docetaxel–ifosfamide combination in anthracycline-pretreated, HER2-negative advanced breast cancer. Therefore, future randomized phase III studies versus single-agent docetaxel or currently established combinations of the latter with other agents in this setting with established clinical activity, such as capecitabine or gemcitabine, will be warranted.

Keywords

Docetaxel Ifosfamide Breast cancer 
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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Christos Kosmas
    • 1
    • 4
  • Nicolas Tsavaris
    • 2
  • Nikolaos Malamos
    • 3
  • George Tsakonas
    • 1
  • Argyris Gassiamis
    • 1
  • Aristidis Polyzos
    • 2
  • Nicolas Mylonakis
    • 1
  • Athanasios Karabelis
    • 1
  1. 1.Department of Medicine, 2nd Division of Medical Oncology“Metaxa” Cancer HospitalPiraeusGreece
  2. 2.Medical Oncology Unit, Departments of Pathophysiology and Propedeutic MedicineAthens University School of Medicine, Laikon General HospitalAthensGreece
  3. 3.Oncology UnitHelena-Venizelou HospitalAthensGreece
  4. 4.Department of Medicine, 2nd Division of Medical Oncology“Metaxa” Cancer HospitalAthensGreece

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