Metronomic cyclophosphamide and capecitabine combined with bevacizumab in advanced breast cancer.

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J Clin Oncol. 2008 Oct 20;26(30):4899-905. Epub 2008 Sep 15.

Metronomic cyclophosphamide and capecitabine combined with bevacizumab in advanced breast cancer.
Dellapasqua S, Bertolini F, Bagnardi V, Campagnoli E, Scarano E, Torrisi R, Shaked Y, Mancuso P, Goldhirsch A, Rocca A, Pietri E, Colleoni M.
Senology Research Unit and Division of Medical Oncology, Department of
Medicine, European Institute of Oncology, Milan, Italy.
Metronomic chemotherapy has shown efficacy in patients with metastatic
breast cancer. When used in association with targeted antiangiogenic
drugs, it was more active than metronomic therapy alone in preclinical
and clinical studies. PATIENTS AND METHODS: Patients with advanced
breast cancer were candidates to receive metronomic oral capecitabine
(500 mg thrice daily) and cyclophosphamide (50 mg daily) plus
bevacizumab (10 mg/kg every 2 weeks).
RESULTS: In 46 assessable
patients, we observed one complete response (CR; 2%), 21 partial
responses (PR; 46%), 19 patients (41%) with stable disease (SD), and
five patients (11%) with progressive disease, for an overall response
rate of 48% (95% CI, 33% to 63%). Additional long-term disease
stabilization (SD > or = 24 weeks) occurred in eight patients, for
an overall clinical benefit (CR + PR + SD > or = 24 weeks) of 68%
(95% CI, 51% to 81%). Median time to progression was 42 weeks (95% CI,
26 to 72 weeks). Toxicity was generally mild. Grade 3 or 4
nonhematologic adverse effects included hypertension (n = 8),
transaminitis (n = 2), and nausea/vomiting (n = 2). Higher baseline
circulating endothelial cells (CECs) were correlated with overall
response (P = .02), clinical benefit (P = .01), and improved
progression-free survival (P = .04).
CONCLUSION: Treatment with
metronomic capecitabine and cyclophosphamide in combination with
bevacizumab was effective in advanced breast cancer and was minimally
toxic. The number of baseline CECs significantly correlated with
response and outcome, therefore supporting further studies on this
surrogate marker for the selection of patients to be candidates for
antiangiogenic treatments.