Metronomic chemotherapy dosing-schedules with estramustine and temozolomide act synergistically with anti-VEGFR-2 antibody to cause inhibition of human umbilical venous endothelial cell growth.

Article Details

Citation
Copy to clipboard

Lam T, Hetherington JW, Greenman J, Little S, Maraveyas A

Metronomic chemotherapy dosing-schedules with estramustine and temozolomide act synergistically with anti-VEGFR-2 antibody to cause inhibition of human umbilical venous endothelial cell growth.

Acta Oncol. 2007;46(8):1169-77.

PubMed ID
17851838 [ View in PubMed
]
Abstract

The effects of 'metronomic' or extended chemotherapy dosing schedules (ECS) are mediated through poorly understood anti-angiogenic mechanisms. ECS combined with biological anti-angiogenic agents have produced promising pre-clinical results. MATERIALS AND METHODS: We have expanded the list of agents with an in vitro ECS profile to include the methylating agent temozolomide (Temodal) and the anti-mitotic agent estramustine (Estracyt). These agents were also combined with a specific anti-angiogenic inhibitor IMC-1C11 and a non-specific agent with anti-angiogenic properties, Compound 5h. The in vitro HUVEC ECS model system was optimised and cell proliferation assays undertaken. RESULTS: As a single agent, estramustine inhibited endothelial cell proliferation with an IC50 of 4.5 microM and was active at 10-33% of the maximum tolerated dose (MTD) from clinical schedules, whilst temozolomide had IC50 of 6.6 microM and was active at 1-6% of MTD. In combination, significant synergy was seen with IMC-1C11 in combination with either drug, whilst modest additive effects were observed with Compound 5h. None of the combinations resulted in significant cytotoxicity or apoptosis. DISCUSSION: The results show that ECS of temozolomide and estramustine can be significantly enhanced when combined with specific anti-angiogenic inhibitors in an in vitro HUVEC system.

DrugBank Data that Cites this Article

Drugs