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

Cancer Chemother Pharmacol. 2010 Aug;66(3):425-31. doi: 10.1007/s00280-009-1176-5. Epub 2009 Dec 15.

Abstract

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/m(2) i.v. in a 3-h infusion) on day 1 and ifosfamide (1.5 g/m(2) 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 non-hematological 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.

MeSH terms

  • Adult
  • Aged
  • Anthracyclines / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Docetaxel
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Ifosfamide / administration & dosage
  • Middle Aged
  • Neoplasm Metastasis
  • Neutropenia / chemically induced
  • Paclitaxel / administration & dosage
  • Retrospective Studies
  • Survival Rate
  • Taxoids / administration & dosage
  • Taxoids / pharmacology
  • Treatment Outcome

Substances

  • Anthracyclines
  • Taxoids
  • Docetaxel
  • Paclitaxel
  • Ifosfamide