Format

Send to:

Choose Destination
See comment in PubMed Commons below
Cancer Lett. 2006 Nov 28;244(1):129-35. Epub 2006 Jan 19.

Potentiation of cyclophosphamide chemotherapy using the anti-angiogenic drug thalidomide: importance of optimal scheduling to exploit the 'normalization' window of the tumor vasculature.

Author information

  • 1Laboratory of Biomedical Magnetic Resonance, Universit√© Catholique de Louvain, B-1200 Brussels, Belgium.

Abstract

The aim of this work was to study how administration schedule affects potentiation of cyclophosphamide, an alkylating agent, by thalidomide, an anti-angiogenic agent. Tumor oxygenation after thalidomide administration was determined over time by EPR oximetry. Such measurements provide a surrogate marker for determining the timing of 'normalization' of tumor vasculature. Re-growth delays were measured using different combinations and schedules of treatments. Additionally, the uptake of the metabolite of cyclophosphamide (hydroxycyclophosphamide or OH-CP) into tumors was determined by high performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS). A significant increase in pO(2) was observed after 2 and 3 days of treatment before eventually declining on day 4. Thalidomide potentiated the effect of cyclophosphamide only when cyclophosphamide was administered after 2 days of treatment with thalidomide (no significant benefit using other schedules). In this time frame, the HPLC/MS/MS measurements showed that the quantity of OH-CP penetrating into the tumor was about twice in mice treated by thalidomide compared to controls. In conclusion, the present study demonstrates that the benefit of combined therapy using an anti-angiogenic agent with a cytotoxic agent requires knowledge of the time window during which the vessels initially become normalized.

PMID:
16426744
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk