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.

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.

• Authors: D Crivellari, D Lombardi, G Corona, C Massacesi, R Talamini, R Sorio, M D Magri, C Lestuzzi, A Lucenti, A Veronesi, G Toffoli
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 17 Issue 5 Pg. 807-12 (May 2006) ISSN: 0923-7534 [Print] England
• PMID: 16497825 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

• Antibiotics, Antineoplastic
• idarubicinol
• Idarubicin
• Daunorubicin

Topics

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