- 1: Ann Oncol. 2006 Feb;17(2):232-8. Epub 2005 Dec 1.
low-dose oral cyclophosphamide and methotrexate plus or minus
thalidomide in metastatic breast cancer: antitumor activity and
Colleoni M, Orlando L, Sanna G, Rocca A, Maisonneuve P, Peruzzotti G, Ghisini R, Sandri MT, Zorzino L, Nolè F, Viale G, Goldhirsch A.
of Medical Oncology, University of Milan School of Medicine, European
Institute of Oncology, Milan, Italy.
We previously demonstrated efficacy and impact on serum vascular
endothelial growth factor (VEGF) for metronomic cyclophosphamide (C)
and methotrexate (M) in patients with breast cancer. New metronomic
schedules were investigated.
PATIENTS AND METHODS: Patients with
advanced breast cancer were randomized to receive oral C (50 mg daily)
and M (2.5 mg twice daily on days 1 and 4) (arm A) or the same regimen
plus thalidomide (200 mg daily) (arm B).
RESULTS: The mean VEGF level
decreased from 378.9 (+/-274.4) pg/ml at baseline to 305.9 (+/-203.6)
pg/ml at 2 months (P<0.001), with similar change with respect to
baseline in both arms. In 171 evaluable patients we observed three
complete remissions (CR) in both arms A and B, 15 partial remission
(PR) in arm A and seven in arm B, for an overall response of 20.9% [95%
confidence interval (CI) 12.9% to 31%] in arm A and 11.8% (95% CI 5.8%
to 20.6%) in arm B. The clinical benefit (CR+PR+SD>or=24 weeks) was
41.5% for both arms. Toxicity was generally mild. Higher neurological
toxicity (2% versus 60%; P<0.0001) and constipation (8% versus 51%;
P<0.0001) was observed in arm B.
CONCLUSIONS: Metronomic low-dose CM
induced a drop in VEGF, and was effective and minimally toxic. The
addition of thalidomide did not improve results.