Metronomic Chemotherapy: Changing the Paradigm That More Is Better

Tumor Angiogenesis: Therapeutic Implications

1971 • 9,898 citations

Isolation of Putative Progenitor Endothelial Cells for Angiogenesis

1997 • 8,673 citations

Patterns and Emerging Mechanisms of the Angiogenic Switch during Tumorigenesis

1996 • 6,878 citations

Mechanisms of angiogenesis

1997 • 5,696 citations

Impaired recruitment of bone-marrow–derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth

2001 • 1,874 citations

VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells

1999 • 1,852 citations

Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer.

2000 • 1,536 citations

Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients

2006 • 1,180 citations

Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity

2000 • 1,159 citations

Signals leading to apoptosis-dependent inhibition of neovascularization by thrombospondin-1

2000 • 992 citations

Vascular and haematopoietic stem cells: novel targets for anti-angiogenesis therapy?

2002 • 685 citations

Phase II Clinical Trial of Bevacizumab and Low-Dose Metronomic Oral Cyclophosphamide in Recurrent Ovarian Cancer: A Trial of the California, Chicago, and Princess Margaret Hospital Phase II Consortia

2007 • 545 citations

Thrombospondin‐1 as an endogenous inhibitor of angiogenesis and tumor growth

2002 • 534 citations

Inhibition of angiogenesis and breast cancer in mice by the microtubule inhibitors 2-methoxyestradiol and taxol.

1997 • 525 citations

Low-dose oral methotrexate and cyclophosphamide in metastatic breast cancer: antitumor activity and correlation with vascular endothelial growth factor levels

2002 • 494 citations

A Multitargeted, Metronomic, and Maximum-Tolerated Dose “Chemo-Switch” Regimen is Antiangiogenic, Producing Objective Responses and Survival Benefit in a Mouse Model of Cancer

2004 • 479 citations

Maximum tolerable dose and low-dose metronomic chemotherapy have opposite effects on the mobilization and viability of circulating endothelial progenitor cells.

2003 • 458 citations

Inhibition of tumor angiogenesis as a strategy to circumvent acquired resistance to anti‐cancer therapeutic agents

1991 • 441 citations

Protracted low-dose effects on human endothelial cell proliferation and survival in vitro reveal a selective antiangiogenic window for various chemotherapeutic drugs.

2002 • 433 citations

Resting and activated endothelial cells are increased in the peripheral blood of cancer patients

2001 • 426 citations

Thrombospondin 1, a mediator of the antiangiogenic effects of low-dose metronomic chemotherapy

2003 • 416 citations

Genetic heterogeneity of the vasculogenic phenotype parallels angiogenesis

2005 • 331 citations

Systemic Chemotherapy for Advanced Non-Small Cell Lung Cancer: Recent Advances and Future Directions

2008 • 328 citations

Lymphoma-Specific Genetic Aberrations in Microvascular Endothelial Cells in B-Cell Lymphomas

2004 • 317 citations

Antitumor effects in mice of low-dose (metronomic) cyclophosphamide administered continuously through the drinking water.

2002 • 313 citations

Antiangiogenesis Is Produced by Nontoxic Doses of Vinblastine

1999 • 271 citations

Optimal biologic dose of metronomic chemotherapy regimens is associated with maximum antiangiogenic activity

2005 • 256 citations

Circulating endothelial-cell kinetics and viability predict survival in breast cancer patients receiving metronomic chemotherapy

2006 • 253 citations

Differences in therapeutic indexes of combination metronomic chemotherapy and an anti-VEGFR-2 antibody in multidrug-resistant human breast cancer xenografts.

2002 • 241 citations

Highly Efficacious Nontoxic Preclinical Treatment for Advanced Metastatic Breast Cancer Using Combination Oral UFT-Cyclophosphamide Metronomic Chemotherapy

2006 • 228 citations

Inhibition of in vitro vascular endothelial cell proliferation and in vivo neovascularization by low‐dose methotrexate

1989 • 202 citations

Thrombospondin-1 Associated with Tumor Microenvironment Contributes to Low-Dose Cyclophosphamide-Mediated Endothelial Cell Apoptosis and Tumor Growth Suppression

2004 • 184 citations

Randomized Phase II Trial of Letrozole and Letrozole Plus Low-Dose Metronomic Oral Cyclophosphamide As Primary Systemic Treatment in Elderly Breast Cancer Patients

2006 • 184 citations

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

2005 • 183 citations

Low-dose chemotherapy combined with an antiangiogenic drug reduces human glioma growth in vivo.

2001 • 182 citations

Serum vascular endothelial growth factor is often elevated in disseminated cancer.

1997 • 181 citations

Kinetics and viability of circulating endothelial cells as surrogate angiogenesis marker in an animal model of human lymphoma.

2001 • 163 citations

Metronomic therapy with cyclophosphamide and dexamethasone for prostate carcinoma

2003 • 162 citations

Phase I Study of Bevacizumab Added to Fluorouracil- and Hydroxyurea-Based Concomitant Chemoradiotherapy for Poor-Prognosis Head and Neck Cancer

2008 • 155 citations

Antiangiogenic therapy of established tumors in human skin/severe combined immunodeficiency mouse chimeras by anti-endoglin (CD105) monoclonal antibodies, and synergy between anti-endoglin antibody and cyclophosphamide.

2001 • 153 citations

Antiangiogenetic therapy with pioglitazone, rofecoxib, and metronomic trofosfamide in patients with advanced malignant vascular tumors

2003 • 145 citations

A Comparative Analysis of Low-Dose Metronomic Cyclophosphamide Reveals Absent or Low-Grade Toxicity on Tissues Highly Sensitive to the Toxic Effects of Maximum Tolerated Dose Regimens

2004 • 132 citations

Continuous infusion of endostatin inhibits differentiation, mobilization, and clonogenic potential of endothelial cell progenitors.

2003 • 124 citations

Phase II study of metronomic chemotherapy for recurrent malignant gliomas in adults

2007 • 121 citations

Trastuzumab in combination with metronomic cyclophosphamide and methotrexate in patients with HER-2 positive metastatic breast cancer

2006 • 117 citations

Chemotherapeutic drugs—more really is not better

2000 • 113 citations

Low Dose Metronomic Oral Cyclophosphamide for Hormone Resistant Prostate Cancer: A Phase II Study

2007 • 111 citations

High-Dose Celecoxib and Metronomic “Low-dose” Cyclophosphamide Is an Effective and Safe Therapy in Patients with Relapsed and Refractory Aggressive Histology Non–Hodgkin's Lymphoma

2006 • 111 citations

Phase II Clinical Trial Results Involving Treatment with Low-Dose Daily Oral Cyclophosphamide, Weekly Vinblastine, and Rofecoxib in Patients with Advanced Solid Tumors

2006 • 111 citations

Cyclophosphamide-methotrexate ‘metronomic’ chemotherapy for the palliative treatment of metastatic breast cancer. A comparative pharmacoeconomic evaluation

2005 • 107 citations

Circulating Angiogenic Cytokines in Patients with Advanced Non-Small Cell Lung Cancer: Correlation with Treatment Response and Survival

2005 • 103 citations

Prolonged clinical benefit with metronomic chemotherapy in patients with metastatic breast cancer

2006 • 102 citations

Pioglitazone and rofecoxib combined with angiostatically scheduled trofosfamide in the treatment of far‐advanced melanoma and soft tissue sarcoma

2004 • 99 citations

Inhibition of Bladder Tumor Growth by 1,1-Bis(3′-Indolyl)-1-(p-Substitutedphenyl)Methanes: A New Class of Peroxisome Proliferator-Activated Receptor γ Agonists

2006 • 95 citations

Combining Agents that Target the Tumor Microenvironment Improves the Efficacy of Anticancer Therapy

2008 • 90 citations

Combined anti-fetal liver kinase 1 monoclonal antibody and continuous low-dose doxorubicin inhibits angiogenesis and growth of human soft tissue sarcoma xenografts by induction of endothelial cell apoptosis.

2002 • 90 citations

A Pilot Pharmacokinetic and Antiangiogenic Biomarker Study of Celecoxib and Low-dose Metronomic Vinblastine or Cyclophosphamide in Pediatric Recurrent Solid Tumors

2006 • 87 citations

Assessing Tumor Angiogenesis

2004 • 84 citations

A pilot study of metronomic temozolomide treatment in patients with recurrent temozolomide-refractory glioblastoma

2006 • 72 citations

Combined Biodifferentiating and Antiangiogenic Oral Metronomic Therapy is Feasible and Effective in Relapsed Solid Tumors in Children: Single-Center Pilot Study

2006 • 71 citations

Oral low-dose cyclophosphamide in metastatic hormone refractory prostate cancer (MHRPC)

2004 • 70 citations

Combination antiangiogenic therapy: Increased efficacy in a murine model of Wilms tumor

2001 • 68 citations

A novel metronomic chemotherapy regimen of weekly platinum and daily oral etoposide in high-risk non-small cell lung cancer patients

2006 • 57 citations

Metronomic oral low-dose treosulfan chemotherapy combined with cyclooxygenase-2 inhibitor in pretreated advanced melanoma: a pilot study

2003 • 56 citations

Metronomic therapy with cyclophosphamide induces rat lymphoma and sarcoma regression, and is devoid of toxicity

2004 • 53 citations

Final Report of Toxicity and Efficacy of a Phase II Study of Oral Cyclophosphamide, Thalidomide, and Prednisone for Patients with Relapsed or Refractory Multiple Myeloma: A Hoosier Oncology Group Trial, HEM01-21

2007 • 53 citations

Cyclophosphamide "metronomic" chemotherapy for palliative treatment of a young patient with advanced epithelial ovarian cancer

2007 • 41 citations

Inhibition of angiogenesis by the antineoplastic agents mitoxantrone and bisantrene

1986 • 41 citations

Low-dose metronomic, multidrug therapy with the PEP-C oral combination chemotherapy regimen for mantle cell lymphoma

2008 • 41 citations

Angiostatic activity of anticancer agents in the chick embryo chorioallantoic membrane (CHE-CAM) assay

1992 • 40 citations

Antiangiogenic Therapy With Pioglitazone, Rofecoxib, and Trofosfamide in a Patient With Endemic Kaposi Sarcoma

2004 • 39 citations

A phase II trial of continuous low-dose oral cyclophosphamide and celecoxib in patients with renal cell carcinoma

2006 • 38 citations

Cyclooxygenase-2 inhibitors suppress angiogenesis and growth of gastric cancer xenografts

2005 • 34 citations

Concomitant radiotherapy and metronomic temozolomide in pediatric high-risk brain tumors.

2002 • 34 citations

Combining Antiangiogenic Agents with Metronomic Chemotherapy Enhances Efficacy against Late-stage Pancreatic Islet Carcinomas in Mice

2002 • 30 citations

Complete remission of relapsing high-grade angiosarcoma with single-agent metronomic trofosfamide

2006 • 29 citations

Low Dose Carboplatin Combined With Angiostatic Agents Prevents Metastasis in Human Testicular Germ Cell Tumor Xenografts

2003 • 28 citations

Biologic Markers of Angiogenesis: Circulating Endothelial Cells in Patients with Advanced Malignancies Treated on Phase I Protocol with Metronomic Chemotherapy and Celecoxib

2008 • 26 citations

A metronomic schedule of cyclophosphamide combined with PEGylated liposomal doxorubicin has a highly antitumor effect in an experimental pulmonary metastatic mouse model

2007 • 24 citations

Significance of thymidine phosphorylase in metronomic chemotherapy using CPT-11 and doxifluridine for advanced colorectal carcinoma.

2007 • 24 citations

Serum Vascular Endothelial Growth Factor as a Predictive Factor in Metronomic (Weekly) Paclitaxel Treatment for Advanced Head and Neck Cancer

2007 • 23 citations

New Anti-Angiogenic Targeted Therapy in Advanced Renal Cell Carcinoma (RCC):Current Status and Future Prospects

2008 • 20 citations

Changes in vascular endothelial growth factor (VEGF) after chemoendocrine therapy in breast cancer.

2004 • 17 citations

Targeted therapy for metastatic renal cell carcinoma: a home run or a work in progress?

2008 • 15 citations

Metronomic therapy with Cyclophosphamide or Doxorubicin inhibits mouse mammary adenocarcinoma growth and metastasis development

2005 • 5 citations