Multiple cycles of high-dose doxorubicin and cyclophosphamide with G- CSF mobilized peripheral blood progenitor cell support in patients with metastatic breast cancer

A. H. Honkoop, E. Van Der Wall, N. Feller, G. J. Schuurhuis, W. J.F. Van Der Vijgh, E. Boven, C. J. Van Groeningen, G. Giaccone, K. Hoekman, J. B. Vermorken, J. Wagstaff, H. M. Pinedo

Research output: Contribution to journalArticlepeer-review

Abstract

Background: In a previous study we applied doxorubicin and cyclophosphamide in a dose-intensive regimen with GM-CSF to patients with metastatic breast cancer (MBC). That treatment failed to prolong the remission duration compared to conventional-dose chemotherapy. In the present study we escalated the dosages of the same agents to: 1) determine the maximum tolerated dosages (MTD) when given for three cycles with G-CSF mobilised peripheral blood progenitor cell (PBPC) reinfusion and 2) evaluate the antitumour effect of this regimen. Patients and methods: For mobilisation of PBPC, G-CSF 15 μg/kg/day was given subcutaneously (s.c.), and in subsequent cohorts leucapheresis was started on days 3, 4 or 6. The intention was to treat MBC patients with three cycles of doxorubicin and cyclophosphamide at a starting dose of doxorubicin 90 mg/m2 and cyclophosphamide 1000 mg/m2. Dosages were then escalated in subsequent cohorts of at least three patients. In case of dose-limiting mucositis, only the dose of cyclophosphamide was escalated in the next cohort. Results: Twenty-one patients entered this protocol, of which 18 patients received high-dose chemotherapy. The mobilisation of PBPC using G-CSF only was sufficient for three cycles of high-dose chemotherapy in 10 of 21 (47%) patients. Mucositis precluded dose escalation of doxorubicin beyond 110 mg/m2. The MTD in this combination was 110 mg/m2 for doxorubicin, and 4 g/m2 for cyclophosphamide, with haemorrhagic cystitis being the dose- limiting toxicity. The overall response rate was 78% (95% confidence interval (95% CI): 57%-97%), with 22% (95% CI: 3%-41%) complete responses. Conclusion: The MTD of this three cycle high-dose regimen was doxorubicin 110 mg/m2 and cyclophosphamide 4 g/m2 with mucositis and cystitis being dose-limiting toxicities. Although the primary aim was not the evaluation of antitumour effect, this high-dose regimen does not appear to provide an improvement of treatment results in comparison with our previous study with the same drugs at moderately high-dosages without stem cell support.

Original languageEnglish (US)
Pages (from-to)957-962
Number of pages6
JournalAnnals of Oncology
Volume8
Issue number10
DOIs
StatePublished - Oct 1997

Keywords

  • Breast cancer
  • High-dose chemotherapy

ASJC Scopus subject areas

  • Hematology
  • Oncology

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