Metronomic low-dose oral cyclophosphamide and methotrexate plus or minus thalidomide in metastatic breast cancer: Antitumor activity and biological effects

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Abstract

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 ≥ 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.

Original languageEnglish
Pages (from-to)232-238
Number of pages7
JournalAnnals of Oncology
Volume17
Issue number2
DOIs
Publication statusPublished - Feb 2006

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Thalidomide
Methotrexate
Cyclophosphamide
Breast Neoplasms
Vascular Endothelial Growth Factor A
Confidence Intervals
Poisons
Constipation
Appointments and Schedules
Serum

Keywords

  • Angiogenesis
  • Breast cancer
  • Cyclophosphamide
  • Methotrexate
  • Metronomic chemotherapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

@article{c3cb264566bc480caeeea8c76ebd9251,
title = "Metronomic low-dose oral cyclophosphamide and methotrexate plus or minus thalidomide in metastatic breast cancer: Antitumor activity and biological effects",
abstract = "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 ≥ 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.",
keywords = "Angiogenesis, Breast cancer, Cyclophosphamide, Methotrexate, Metronomic chemotherapy",
author = "Marco Colleoni and L. Orlando and G. Sanna and A. Rocca and P. Maisonneuve and G. Peruzzotti and R. Ghisini and Sandri, {M. T.} and L. Zorzino and F. Nol{\`e} and G. Viale and A. Goldhirsch",
year = "2006",
month = "2",
doi = "10.1093/annonc/mdj066",
language = "English",
volume = "17",
pages = "232--238",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "NLM (Medline)",
number = "2",

}

TY - JOUR

T1 - Metronomic low-dose oral cyclophosphamide and methotrexate plus or minus thalidomide in metastatic breast cancer

T2 - Antitumor activity and biological effects

AU - Colleoni, Marco

AU - Orlando, L.

AU - Sanna, G.

AU - Rocca, A.

AU - Maisonneuve, P.

AU - Peruzzotti, G.

AU - Ghisini, R.

AU - Sandri, M. T.

AU - Zorzino, L.

AU - Nolè, F.

AU - Viale, G.

AU - Goldhirsch, A.

PY - 2006/2

Y1 - 2006/2

N2 - 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 ≥ 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.

AB - 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 ≥ 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.

KW - Angiogenesis

KW - Breast cancer

KW - Cyclophosphamide

KW - Methotrexate

KW - Metronomic chemotherapy

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U2 - 10.1093/annonc/mdj066

DO - 10.1093/annonc/mdj066

M3 - Article

C2 - 16322118

AN - SCOPUS:31544441697

VL - 17

SP - 232

EP - 238

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 2

ER -