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CD 1, Track 8

DR RUGO: In addition to evaluating the combination of capecitabine/bevacizumab, another research strategy is to combine endocrine therapy with bevacizumab. Some interesting data indicate that estrogen may directly modulate angiogenesis through effects on endothelial cells in both physiologic and pathologic conditions. We also have data indicating that antiestrogen therapy blocks VEGF expression and estrogen-induced angiogenesis may be blocked by antiestrogen therapy.

Rakesh Jain’s group in Boston has observed an androgen-dependent tumor model and shown that castration, interestingly, leads to initial vascular regression, and then a second wave of angiogenesis occurs with vascular regrowth in this murine tumor model.

So a hypothesis was generated that anti-VEGF therapy may overcome this resistance of the second wave of angiogenesis seen with endocrine therapy in animal models and could improve the efficacy of standard hormone therapy in hormone receptor-positive metastatic breast cancer.

In the study presented by Dr Traina at ASCO this year, 43 patients received bevacizumab at 15 mg/kg every three weeks and letrozole at 2.5 mg per day. The combination appeared to be well tolerated. The drug-related toxicities were expected and only seen in a small number of patients. The efficacy analysis, which wasn’t the primary goal, was confounded by the long duration of prestudy aromatase inhibitor therapy in most patients, although it did appear that a number might have benefited from the therapy.

We have planned a Phase III study within CALGB and the Intergroup in patients with hormone receptorpositive disease. The patients will be randomly assigned to endocrine therapy with placebo or bevacizumab (administered every three weeks) as first-line therapy.

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