Letrozole Plus Oral Cyclophosphamide Plus/Minus Sorafenib as Primary Systemic Treatment in Breast Cancer Patients
Status:
Unknown status
Trial end date:
2010-12-01
Target enrollment:
Participant gender:
Summary
Endocrine therapy is the mainstay of systemic treatment in patients with endocrine responsive
breast cancer. Aromatase inhibitors are the most active agents in post-menopausal women.
Randomized comparisons either in primary/adjuvant setting or in metastatic disease setting
have demonstrated the superiority of these drugs over tamoxifen.
Primary systemic treatment administered to breast cancer patients is a useful model to
identify baseline features able to predict which patients are most likely to benefit from
cytotoxic treatment and is a way to study new biological markers in relation to the
predictive information they provide.
This treatment modality represents therefore the best way to explore new treatment strategies
in particular treatment strategies involving target therapies.
We have conducted a randomised phase II trial in which the activity of Letrozole plus/minus
oral metronomic cyclophosphamide as primary systemic treatment has been investigated in a
patient population of elderly breast cancer patients. The conclusions were that the
combination of letrozole with metronomic cyclophosphamide was a very active scheme. In
addition this was the first study demonstrating in vivo the antiangiogenic effect of
metronomic scheduling. This study suggests that chemotherapy administered on a metronomic
schedule, targeting therefore the neo-angiogenesis, could be synergistic with endocrine
therapy with aromatase inhibitors.
Sorafenib is a multi-kinase inhibitor targeting Raf, VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-alfa,
Flt-3, c-Kit, and p38.
There is a strong rationale of combining different anti-angiogenic agents. At the ASCO 2007
meeting the data of a phase I study exploring the toxicity of a combination of sorafenib and
bevacizumab have been presented. The results showed an increased toxicity being dose limiting
in some patients. To our knowledge there are no data un activity and toxicity of adding
sorafenib to metronomic chemotherapy.