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Optimal low-dose metronomic chemotherapy and antiangiogenic activity

Shaked Y et al. (2005) The optimal biological dose of metronomic chemotherapy regimens is associated with maximum antiangiogenic activity. Blood [10.1182/blood-2005-04-1422]

Results from an animal study have indicated that measuring the levels of circulating VEGF-receptor-2-positive endothelial progenitor cells, or CEPs, might help to determine the optimal biological dose (OBD) in patients undergoing metronomic chemotherapy.

Shaked and co-workers used four different mouse tumor models to assess both the efficacy and the toxicity of four metronomic chemotherapy regimens—cyclophosphamide, vinblastine, vinorelbine and cisplatinum. In each case, low doses of the drugs were administered at regular, short intervals with no prolonged breaks; this type of dosing is believed to maximise the antiangiogenic potential of the treatment. The OBD for each regimen was defined as the dose producing the greatest reduction in tumor volume, with the lowest toxicity. In parallel, the levels of viable CEPs in blood samples taken from the mice following one week of treatment were measured, and compared with those from untreated, control animals.

The analysis revealed a statistically significant, dose-dependent decrease in viable CEPs. For each treatment, the maximum fall in viable CEPs occurred in mice that had received the OBD of the drug, suggesting that the level of circulating CEPs might be a useful indicator of antiangiogenic activity.

The authors discuss the feasibility of translating these findings to the clinical setting, and conclude that “CEPs may serve as a pharmacodynamic biomarker to determine the optimal biological dose of metronomic chemotherapy regimens”.


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Kirby, R. Optimal low-dose metronomic chemotherapy and antiangiogenic activity. Nat Rev Clin Oncol 2, 489 (2005).

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