Increased tumor oxygenation and drug uptake during anti-angiogenic weekly low dose cyclophosphamide enhances the anti-tumor effect of weekly tirapazamine.

ABSTRACT: Metronomic cyclophosphamide treatment is associated with anti-angiogenic activity and is anticipated to generate exploitable hypoxia using hypoxia-activated prodrugs. Weekly administration of tirapazamine (TPZ; 5 mg/kg body weight i.p.) failed to inhibit the growth of 9L gliosarcoma tumors grown s.c. in scid mice. However, the anti-tumor effect of weekly cyclophosphamide (CPA) treatment (140 mg/kg BW i.p.) was substantially enhanced by weekly TPZ administration. An extended tumor free period and increased frequency of tumor eradication without overt toxicity were observed when TPZ was given 3, 4 or 5 days after each weekly CPA treatment. Following the 2(nd) CPA injection, Electron Paramagnetic Resonance (EPR) Oximetry indicated significant increases in tumor pO(2), starting at 48 hr, which

SUBMITTER: Doloff JC 

PROVIDER: S-EPMC2912211 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature