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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.

AbstractBACKGROUND:
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.
AuthorsC Campisi, A Fabi, P Papaldo, S Tomao, B Massidda, A Zappala, M T Ionta, F Cognetti
JournalAnnals 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
PMID9653499 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Vinblastine
  • Vinorelbine
  • Ifosfamide
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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