A phase I trial of high-dose paclitaxel, cyclophosphamide and mitoxantrone with autologous blood stem cell support for the treatment of metastatic breast cancer

S. Glück, C. Germond, P. Lopez, P. Cano, M. Dorreen, T. Koski, A. Arnold, H. Dulude, G. Gallant

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

The aim of this phase I study was to determine the dose limiting toxicity (DLT), maximum tolerated dose (MTD) and efficacy of a new combination of cyclophosphamide (6 g/m2), mitoxantrone (70 mg/m2), with dose escalation of paclitaxel (Taxol®) at a starting dose of 250 mg/m2 given intravenously over 3 h in a transplantation setting. Patients with metastatic breast cancer and chemosensitive disease were eligible. The autologous blood stem cell re-infusion and subsequent recovery occurred in an outpatient setting. 50 patients were enrolled, but 10 withdrew. 40 completed the entire protocol. At 400mg/m2 paclitaxel administered over 3h, 3 of 6 patients experienced serious adverse events: approximately 20-40 min after completion of infusion, diaphoresis, bradycardia mild hypotension and diarrhoea occurred; 2 patients lost consciousness for a few minutes. An extended infusion schedule delivering 400mg/m2 paclitaxel over 6 h rather than 3 h was initiated at this level without patients experiencing this DLT. At the next dose of 450 mg/m2 paclitaxel over 6 h, the same DLT was seen as at 400 mg/m2 paclitaxel over 3h and, therefore, MTD was reached. Time to recovery for the absolute neutrophil count ≤ 0.5 x 109/1 was 10-19 days (median 12 days); and for platelets ≤ 20 x 109/1 was 18-20 days (median 11.5 days). 21 patients developed neutropenic fever that required intravenous antibiotics and re-admission; the transfusion frequency for packed red blood cell was 0-5 units (median 2 units) and for platelets, 1-5 encounters (median 2). 13 complete responses, 1 patient with no evidence of disease and 19 partial remissions were documented. The dose of 400 mg/m2 at an infusion rate of 6h will be used for the ongoing phase II study to evaluate efficacy and toxicity further.

Original languageEnglish (US)
Pages (from-to)1008-1014
Number of pages7
JournalEuropean Journal of Cancer
Volume34
Issue number7
DOIs
StatePublished - Jun 1 1998

Keywords

  • ABSC
  • Breast cancer
  • Combination chemotherapy
  • Metastatic
  • Paclitaxel
  • Phase I
  • Taxoid

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

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