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.
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.


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.


CONCLUSIONS
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.
Division of Medical Oncology C, Centro di Riferimento Oncologico, Aviano, Italy. dcrivellari@cro.it
D
D
Crivellari
D
D
Lombardi
G
G
Corona
C
C
Massacesi
R
R
Talamini
R
R
Sorio
M D
MD
Magri
C
C
Lestuzzi
A
A
Lucenti
A
A
Veronesi
G
G
Toffoli
D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D001859:Bone Neoplasms / Q000097:blood / Q000188:drug therapy / Q000556:secondary; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D003630:Daunorubicin / Q000031:analogs & derivatives / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage*; D008113:Liver Neoplasms / Q000097:blood / Q000188:drug therapy / Q000556:secondary; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy / Q000556:secondary; D012983:Soft Tissue Neoplasms / Q000097:blood / Q000188:drug therapy / Q000556:secondary
D000903:Antibiotics, Antineoplastic; C054440:idarubicinol; D015255:Idarubicin; D003630:Daunorubicin