BACKGROUND: 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.
RCT Entities:
BACKGROUND: 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.
Authors: Shivaani Kummar; Jiuping Ji; Robert Morgan; Heinz-Josef Lenz; Shannon L Puhalla; Chandra P Belani; David R Gandara; Deborah Allen; Brian Kiesel; Jan H Beumer; Edward M Newman; Larry Rubinstein; Alice Chen; Yiping Zhang; Lihua Wang; Robert J Kinders; Ralph E Parchment; Joseph E Tomaszewski; James H Doroshow Journal: Clin Cancer Res Date: 2012-02-03 Impact factor: 12.531
Authors: Leandro E Mainetti; Viviana R Rozados; Ana Rossa; R Daniel Bonfil; O Graciela Scharovsky Journal: J Cancer Res Clin Oncol Date: 2010-03-27 Impact factor: 4.553
Authors: N Penel; S Clisant; E Dansin; C Desauw; M Dégardin; L Mortier; M Vanhuyse; F Bonodeau; C Fournier; J-L Cazin; A Adenis Journal: Br J Cancer Date: 2010-03-30 Impact factor: 7.640
Authors: K K Y Cham; J H E Baker; K S Takhar; J A Flexman; M Q Wong; D A Owen; A Yung; P Kozlowski; S A Reinsberg; E M Chu; C-W A Chang; A K Buczkowski; S W Chung; C H Scudamore; A I Minchinton; D T T Yapp; S S W Ng Journal: Br J Cancer Date: 2010-06-08 Impact factor: 7.640