Ifosfamide given by continuous-intravenous infusion in association with vinorelbine in patients with anthracycline- resistant metastatic breast cancer: A phase I-II clinical trial

C. Campisi, A. Fabi, P. Papaldo, S. Tomao, B. Massidda, A. Zappala, M. T. Ionta, F. Cognetti

Research output: Contribution to journalArticle

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 g/m2 on days 13 + 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 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.

Original languageEnglish
JournalCancer Chemotherapy and Pharmacology
Volume44
Issue numberSUPPL.
DOIs
Publication statusPublished - 1999

Fingerprint

Ifosfamide
Phase II Clinical Trials
Clinical Trials, Phase I
Anthracyclines
Intravenous Infusions
Breast Neoplasms
Toxicity
Taxoids
Pharmacokinetics
Chemotherapy
vinorelbine
Poisons
Sodium
Therapeutics
Neutropenia
Outpatients

Keywords

  • Ifosfamide
  • Metastatic breast cancer
  • Vinorelbine

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Oncology

Cite this

Ifosfamide given by continuous-intravenous infusion in association with vinorelbine in patients with anthracycline- resistant metastatic breast cancer : A phase I-II clinical trial. / Campisi, C.; Fabi, A.; Papaldo, P.; Tomao, S.; Massidda, B.; Zappala, A.; Ionta, M. T.; Cognetti, F.

In: Cancer Chemotherapy and Pharmacology, Vol. 44, No. SUPPL., 1999.

Research output: Contribution to journalArticle

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title = "Ifosfamide given by continuous-intravenous infusion in association with vinorelbine in patients with anthracycline- resistant metastatic breast cancer: A phase I-II clinical trial",
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 g/m2 on days 13 + 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 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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year = "1999",
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T1 - Ifosfamide given by continuous-intravenous infusion in association with vinorelbine in patients with anthracycline- resistant metastatic breast cancer

T2 - A phase I-II clinical trial

AU - Campisi, C.

AU - Fabi, A.

AU - Papaldo, P.

AU - Tomao, S.

AU - Massidda, B.

AU - Zappala, A.

AU - Ionta, M. T.

AU - Cognetti, F.

PY - 1999

Y1 - 1999

N2 - 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 g/m2 on days 13 + 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 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.

AB - 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 g/m2 on days 13 + 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 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.

KW - Ifosfamide

KW - Metastatic breast cancer

KW - Vinorelbine

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