Combined 4-hydroxy-ifosfamide and vinorelbine treatment in established and primary human breast cell cultures

L. Ricotti, F. Barzanti, A. Tesei, D. Amadori, A. Gasperi-Campani, G. L. Frassineti, Wainer Zoli

Research output: Contribution to journalArticlepeer-review


Background: Vinorelbine and ifosfamide are active drugs against breast cancer, but the best treatment schedule has yet to be defined by preclinical or clinical studies. The antitumor activity of 4-hydroxy-ifosfamide (4-OH- IF), the active form of ifosfamide, and vinorelbine (VNB) and their interaction were investigated in two established breast cancer cell lines (MCF-7 and BRC-230) and in 10 primary breast cancer cultures. Materials and methods: Cytotoxic activity was evaluated by a highly efficient clonogenic assay (HECA). The median-effect principle was applied to evaluate synergistic and antagonistic interactions and the corresponding combination index values were calculated. Cell cycle perturbations were analyzed by flow cytometry. Results: In MCF-7 and BRC-230 cell lines the sequence VNB for 4 hours followed by 4-OH-IF for 24 hours produced an antagonistic effect. Conversely, the inverse sequential scheme, 4-OH-IF → VNB provided synergistic effects on both cell lines. The synergism was associated with a strong block in the G2-M phase. Synergistic activity of 4-OH-IF → VNB sequence was confirmed in 7 of 10 primary breast cancer cultures. Conclusions: In conclusion, the sequence 4-OH-IF → VNB appeared to be the most effective scheme both in established cell lines and in primary breast cancer cultures.

Original languageEnglish
Pages (from-to)587-594
Number of pages8
JournalAnnals of Oncology
Issue number5
Publication statusPublished - 2000


  • 4-OH-IF
  • Breast cancer
  • Drug combination
  • Human cell lines
  • Primary cultures
  • VNB

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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