Innovative schedule of oral idarubicin in elderly patients with metastatic breast cancer: comprehensive results of a phase II multi-institutional study with pharmacokinetic drug monitoring

Ann Oncol. 2006 May;17(5):807-12. doi: 10.1093/annonc/mdl013. Epub 2006 Feb 23.

Abstract

Background: To determine if protracted low-dose oral idarubicin (IDA), feasible in a previous dose-finding study, would result in similar activity and a better toxicity profile in patients with metastatic breast cancer.

Patients and methods: Elderly women (> or=65 years) with metastatic breast carcinoma were treated with 7.5 mg/day for 21 consecutive days, every 4 weeks. After the first fourteen patients, due to excessive toxicity, the protocol was amended to 5 mg/day. IDA and Idarubicinol (IDOL) plasma concentrations (C(trough)) were investigated in all patients.

Results: Between April 1999 and June 2004, 47 elderly patients were accrued in this two-part study (14 and 33 patients respectively). The median age was 74 and 75 years respectively. Visceral involvement was present in most patients. A partial response was noted in 7/31 patients (22%; 95% CI, 9.6-41.1%). Eleven patients had stable disease (33%). At the dose of 5 mg/day the treatment was well tolerated. Neutropenia grade 4 was present in only 6% of patients; alopecia > grade 1 and cardiotoxicity did not occur. The median time to progression was 3 months and the median overall survival was 17 months. IDA C(trough) and IDOL C(trough) levels were significantly associated with haematologic toxicity.

Conclusion: This study shows that idarubicin at the dose of 5 mg/day for 21 consecutive days is feasible and effective in elderly breast cancer patients but do not demonstrate an improvement in efficacy. A determination of the IDA and IDOL plasma levels (C(trough)) is predictive for toxicity.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Antibiotics, Antineoplastic / administration & dosage*
  • Bone Neoplasms / blood
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / secondary
  • Breast Neoplasms / blood
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Chromatography, High Pressure Liquid
  • Daunorubicin / analogs & derivatives
  • Daunorubicin / blood
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Monitoring
  • Female
  • Humans
  • Idarubicin / administration & dosage*
  • Liver Neoplasms / blood
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / secondary
  • Lung Neoplasms / blood
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / secondary
  • Soft Tissue Neoplasms / blood
  • Soft Tissue Neoplasms / drug therapy
  • Soft Tissue Neoplasms / secondary

Substances

  • Antibiotics, Antineoplastic
  • idarubicinol
  • Idarubicin
  • Daunorubicin