Annals of Oncology 9:565-567, 1998
© 1998 European Society for Medical Oncology
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Ifosfamide given by continuous-intravenous infusion in association with vinorelbine in patients with anthracycline-resistant metastatic breast cancer: A phase I–II clinical trial
1National Research Council, Institute of Biomedical Technologies Rome
2First Department of Medical Oncology, Regina Elena Cancer Insitute Rome
3National Institute for Cancer Research Genoa
4Medical Oncology Institute, University of Cagliari Cagliari
5Fourth General Surgery Institute, ‘La Sapienza’ University of Rome Italy
Correspondence to: Francesco Cognetti, MD Divisione Oncologia Medica I Istituto Regina Elena, Viale Regina Elena 291 00161 Roma Italy
BACKGROUND: Vinorelbine (VNR) is highly active in metastatic breast cancer (MBC) and has shown an overall response rate of 40%-50% as first-line treatment. In vitro, a synergy has been observed between this drug and ifosfamide (IFX). In addition, the pharmacokinetics of IFX suggest that it may have greater activity when given by continuous-intravenous infusion (C.I.V.I.). The aim of this study was. therefore, to assess the antitumor efficacy and toxicity of the combination of bolus VNR and C.I.V.I. IFX as second-line therapy in anthracycline-resistant breast cancer patients.
PATIENTS AND METHODS: Forty-two patients with MBC who had already received anthracycline-based chemotherapy were treated with a regimen consisting of IFX, by C.I.V.I. for 72 hours and bolus VNR. The courses were repeated every three weeks for a maximum of eight cycles. Four dose intensification steps were planned: IFX, 1.5 g/m2 on days 1–3 + VNR, 30 mg/m2 on day 1 (six patients); IFX, 2 g/m2 on days 1–3 + VNR, 25 mg/m2 on day 1 (six patients); IFX, 1.8 mg/m2 on days 1–3 + VNR, 25 mg/m2 on days 1 and 8 (six patients); IFX, 2 g/m2 on days 1–3 + VNR, 25 mg/m2 on days 1 and 8 (24 patients). Sodium-2-mercaptoethane sulfonate (mesna) was associated with IFX at an infusion ratio of 1:1 and, once the infusion was completed, per os every four hours for three times.
RESULTS: All of the 42 patients entered were assessable for toxicity, and 41 of them for response. Neutropenia was the most frequently-occurring toxicity, but only five patients at the highest dose level (11.9%) presented grade 4, and none of those at the first three steps. Other significant toxic effects were mild (only grade I–II). The median relative dose intensity was 95% at the highest dose level and all of the treatments were administered on an out-patient basis. The overall response rate was 36.5% with a CR rate of 4.8% (two of 41 patients, all at the highest dose level) and a PR rate of 31.7% (13 of 41 patients). The median response duration was 7.0 months (range 2–13 months).
CONCLUSIONS: The present phase I–II study shows that the IFX and VNR combination is an active and well-tolerated treatment in MBC and provides an alternative to taxanes for patients previously treated with anthracyclines.
ifosfamide, metastatic breast cancer, vinorelbine
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