Tumor antivascular effects of radiotherapy combined with combretastatin a4 phosphate in human non-small-cell lung cancer.
OBJECTIVE
The tumor vascular effects of radiotherapy and subsequent administration of the vascular disrupting agent combretastatin A4 phosphate (CA4P) were studied in patients with advanced non-small-cell lung cancer using volumetric dynamic contrast-enhanced computed tomography (CT).


METHODS
Following ethical committee approval and informed consent, 8 patients receiving palliative radiotherapy (27 Gy in six fractions, twice weekly) also received CA4P (50 mg/m(2)) after the second fraction of radiotherapy. Changes in dynamic CT parameters of tumor blood volume (BV) and permeability surface area product (PS) were measured for the whole tumor volume, tumor rim, and center after radiotherapy alone and after radiotherapy in combination with CA4P.


RESULTS
After the second fraction of radiotherapy, 6 of the 8 patients showed increases in tumor PS (23.6%, p = 0.011). Four hours after CA4P, a reduction in tumor BV (22.9%, p < 0.001) was demonstrated in the same 6 patients. Increase in PS after radiotherapy correlated with reduction in BV after CA4P (r = 0.77, p = 0.026). At 72 h after CA4P, there was a sustained reduction in tumor BV of 29.4% (p < 0.001). Both increase in PS after radiotherapy and reduction in BV after CA4P were greater at the rim of the tumor. The BV reduction at the rim was sustained to 72 h (51.4%, p = 0.014).


CONCLUSIONS
Radiotherapy enhances the tumor antivascular activity of CA4P in human non-small-cell lung cancer, resulting in sustained tumor vascular shutdown.
Ng
Quan-Sing
QS
Marie Curie Research Wing, Mount Vernon Hospital, Middlesex, United Kingdom.
Goh
Vicky
V
Carnell
Dawn
D
Meer
Khalda
K
Padhani
Anwar R
AR
Saunders
Michele I
MI
Hoskin
Peter J
PJ
D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D001810:Blood Volume / Q000187:drug effects / Q000528:radiation effects; D002199:Capillary Permeability / Q000187:drug effects / Q000528:radiation effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000188:drug therapy / Q000532:radiotherapy; D003131:Combined Modality Therapy; D003287:Contrast Media; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000532:radiotherapy; D008297:Male; D013267:Stilbenes / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed / Q000379:methods
D000972:Antineoplastic Agents, Phytogenic; D003287:Contrast Media; D013267:Stilbenes; C058728:fosbretabulin