L. Ricotti et al., Combined 4-hydroxy-ifosfamide and vinorelbine treatment in established andprimary human breast cell cultures, ANN ONCOL, 11(5), 2000, pp. 587-594
Background: Vinorelbine and ifosfamide are active drugs against breast canc
er, 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 interactio
n 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 efficie
nt clonogenic assay (HECA). The median-effect principle was applied to eval
uate synergistic and antagonistic interactions and the corresponding combin
ation index values were calculated. Cell cycle perturbations were analysed
by flow cytometry.
Results: In MCF-7 and BRC-230 cell lines the sequence VNB for 4 hours follo
wed by 4-OH-IF for 24 hours produced an antagonistic effect. Conversely, th
e inverse sequential scheme, 4-OH-IF --> VNB provided synergistic effects o
n 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.