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Table 1 Preclinical studies on combinations of anti-vascular endothelial growth factor (VEGF) drugs with conventional therapies, or other therapeutics

From: Combination therapy in cancer: effects of angiogenesis inhibitors on drug pharmacokinetics and pharmacodynamics

Tumor model Drugs Treatment schedule Effects of AI ST measurement Ref.
Name Type Angiogenesis inhibitor (AI) Subsequent treatment (ST) Time of AI before ST Time of biopsy after ST Tumor vasculature Tumor drug uptake
NB-1691 Neuroblastoma Bevacizumab ≈ 8 mg/kg Topotecan, etoposide −7 days 1 h ↓ vessel density ↓ permeability ↓ necrosis = topotecan HPLC [20]
−3 days ↓ vessel density ↓ permeability ↑ perfusion ↑ topotecan =/↑ etoposide
−1 day ↓ vessel density ↓ permeability ↑ perfusion =/↑ topotecan ↑ etoposide
0 day   = topotecan = etoposide
SK-N-AS Neuroblastoma Bevacizumab ≈ 8 mg/kg Topotecan −7 days 1 h   =/↑ topotecan  
−3 days ↑ topotecan
−1 day = topotecan
0 day = topotecan
DM443 Melanoma Bevacizumab 5 mg/kg Melphalan −3 days 1 day ↓ perfusion/permeability = vessel density ↑ melphalan IHC of DNA-melphalan adduct [34]
DM738 Melanoma Bevacizumab 5 mg/kg Melphalan −3 days 1 day ↓ perfusion/permeability = vessel density ↑ melphalan
SAS Head and neck cancer Bevacizumab ≈ 10 mg/kg BPA −7 days 1 h   = BPA PGA [66]
−3 days ↓ vessel density = BPA
−1 day ↑ perfusion/permeability ↑ BPA
−0.5 day   ↑ BPA
HCCLM3 Hepatic cancer Bevacizumab 5 mg/kg Doxorubicin −7 days 1 h ↓ vessel density = doxorubicin HPLC [67]
−5 days ↑ doxorubicin
−3 days ↑ doxorubicin
−1 day = doxorubicin
0 day = doxorubicin
MX-1 Breast cancer Bevacizumab 5 mg/kg Paclitaxel −1 h 2 days ↓ perfusion/permeability ↑ paclitaxel HPLC [68]
A549 Lung cancer Bevacizumab 5 mg/kg Paclitaxel −1 h 2 days ↑ paclitaxel
OSC-19 Oral squamos cancer Bevacizumab ≈ 4 mg/kg Cetuximab −3 days From 1 to 13 days ↑ pericyte coverage ↑ cetuximab FM [70]
SCC-1 Oral squamos cancer Bevacizumab ≈ 4 mg/kg Cetuximab −3 days From 1 to 13 days   ↑ cetuximab
U87MG Glioblastoma Bevacizumab 10 mg/kg Temozolomide, irinotecan −7 days 1 h   =/↑ temozolomide =/↑ irinotecan HPLC [71]
0 day   =/↑ temozolomide =/↑ irinotecan
KPL4 Breast cancer Bevacizumab 10 mg/kg Trastuzumab −7 days 6 h ↓ vessel density ↓ trastuzumab multispectral ultra FM [72]
−3 days ↓ vessel density ↓ trastuzumab
−1 day ↓ vessel density ↓ trastuzumab
KPL4 Breast cancer B20.4.1 10 mg/kg Trastuzumab −1 day From 1 to 7 days ↓ vessel density ↓ perfusion ↓ trastuzumab SPECT [73]
MMTV-HER2 Fo5 Breast cancer B20.4.1 10 mg/kg Trastuzumab −1 day From 1 to 7 days   ↓ trastuzumab
SUM149 Colon cancer Bevacizumab 10 mg/kg Cetuximab, R1507 (Ab a IGF1R) −4 days 3 days ↓ vessel density ↓ R1507 ↓ cetuximab SPECT [74]
SKBR3 Breast cancer Bevacizumab 10 mg/kg R1507 (Ab a IGF1R) −4 days 3 days   ↓ R1507
MDA-MB-435 Breast cancer A461 1 mg/kg Cisplatin + 5-FU −1 day 1 h ↓ perfusion/permeability ↓ vessel density ↑ pericyte coverage ↓ cisplatin = 5-FU ICP-AES (cisplatin) HPLC (5-FU) 75]
SKOV-3 Ovarian cancer Bevacizumab 5 mg/kg Trastuzumab −1, 2, and 5 days 1 and 6 days ↓ trastuzumab PET [76]
OE19 Esophageal cancer Bevacizumab 5 mg/kg Trastuzumab −1, 2, and 5 days 1 and 6 days   ↓ trastuzumab
A2780-1A9 Ovarian cancer Bevacizumab ≈ 6 mg/kg Paclitaxel −5 and −1 days From 0.25 h to 3 days ↓ vessel diameter ↓ perfusion/permeability ↓ necrosis ↓ paclitaxel HPLC MALDI [77]
IGROV1 Ovarian cancer Bevacizumab ≈6 mg/kg Paclitaxel −5 and −1 days 6 h ↓ vessel diameter = paclitaxel
HT-29 Colon cancer Bevacizumab ≈6 mg/kg Paclitaxel −5 and −1 days 6 h ↓ vessel density = paclitaxel
HT29 Colon cancer A461 ≈ 8 mg/kg Irinotecan −7 and −3 days 1 h ↓ vessel number/diameter ↑ perfusion/permeability = necrosis =/↑ irinotecan = SN-38 metabolite HPLC [78]
  1. = equal; ↓ reduction; ↑ increase; =/↓ no significant reduction; =/↑ no significant increase; HPLC high performance liquid chromatography; IHC immunohistochemistry; BPA p-boronophenylalanine; PGA prompt γ-ray spectrometry; FM fluorescence microscopy; SPECT single photon emission computerized tomography; ICP-AES inductively coupled plasma atomic emission spectrometry; 5-FU 5-fluorouracil; PET positron emission tomography; MALDI matrix-assisted laser desorption/ionization