http://annonc.oxfordjournals.org/cgi...tract/mdl013v1
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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
D. Crivellari1*, D. Lombardi1, G. Corona2, C. Massacesi5, R. Talamini3, R. Sorio1, M. D. Magri1,
C. Lestuzzi4, A. Lucenti6, A. Veronesi1 & G. Toffoli2
1Division of Medical Oncology C, Centro di Riferimento Oncologico, Aviano; 2Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico,
Aviano; 3Epidemiology and Biostatistic Unit, Centro di Riferimento Oncologico, Aviano; 4Cardiology Unit, Centro di Riferimento Oncologico, Aviano;
5Division of Medical Oncology, Umberto Io Hospital, Ancona; 6Division of Medical Oncology, General Hospital, Trento, Italy
Received 10 November 2005; revised 6 January 2006; accepted 9 January 2006
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 (‡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 (Ctrough) 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 Ctrough and IDOL Ctrough 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 (Ctrough) is predictive for toxicity.
"In conclusion, even though our results with this new oral drug schedule confirm previous data on the activity of IDA but do not demonstrate an improvement in efficacy, the opportunity to utilise the schedule should not be underestimated."