Continuous low-dose (metronomic) chemotherapy on rat prostate tumors evaluated using MRI in vivo and comparison with histology

Dawen Zhao, Lan Jiang, Eric W. Hahn, Ralph P. Mason

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Continuous low-dose (metronomic) therapy, based on cyclophosphamide (CTX) combined with thalidomide (Tha), was evaluated on Dunning prostate R3327-AT1 rat tumors. Significantly delayed tumor growth (P < .001) was observed with oral CTX alone at a low dose (metronomic cyclophosphamide or M-CTX; 30 mg/kg per day) or combined with Tha. To investigate dynamic changes in tumor physiology during early stages of treatment, magnetic resonance imaging (MRI) was applied before and during the M-CTX or M-CTX + Tha therapy. Dynamic contrast-enhanced MRI revealed significant changes in the tumor center by day 3 (P < .01); by day 7, only a thin peripheral tumor region showed high signal enhancement. There was a significant correlation between poorly enhancing fraction on day 7 and ultimate tumor growth delay (P < .02). The apparent transverse relaxation rate (R2*) showed similar baseline tumor heterogeneity, but no obvious changes with growth or therapy. Histology confirmed substantial necrosis in the tumor center, leaving a thin live peripheral rim. Immunohistochemistry showed a significant increase in vascular endothelial growth factor, and apoptotic tumor and vascular endothelial cells. These results show the efficacy of the metronomic CTX ± Tha for delaying tumor growth and indicate that MRI provides insights into the mode of action and early indication of efficacy.

Original languageEnglish (US)
Pages (from-to)678-687
Number of pages10
JournalNeoplasia
Volume7
Issue number7
DOIs
Publication statusPublished - Jul 2005

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Keywords

  • Anti-angiogenesis
  • Continuous low-dose (metronomic) chemotherapy
  • Immunohistochemistry
  • Magnetic resonance imaging (MRI)
  • Prostate tumor

ASJC Scopus subject areas

  • Cancer Research

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