Abstract | 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.
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Authors | C Campisi, A Fabi, P Papaldo, S Tomao, B Massidda, A Zappala, M T Ionta, F Cognetti |
Journal | Annals of oncology : official journal of the European Society for Medical Oncology
(Ann Oncol)
Vol. 9
Issue 5
Pg. 565-7
(May 1998)
ISSN: 0923-7534 [Print] England |
PMID | 9653499
(Publication Type: Clinical Trial, Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Vinblastine
- Vinorelbine
- Ifosfamide
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Topics |
- Adult
- Aged
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- Breast Neoplasms
(drug therapy, pathology)
- Dose-Response Relationship, Drug
- Drug Administration Schedule
- Drug Resistance, Neoplasm
- Female
- Humans
- Ifosfamide
(administration & dosage)
- Infusions, Intravenous
- Middle Aged
- Treatment Outcome
- Vinblastine
(administration & dosage, analogs & derivatives)
- Vinorelbine
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