Tumor antivascular effects of radiotherapy combined with combretastatin A4 phosphate in human non-small-cell lung cancer

Purpose: 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). Patients and 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). Conclusion: Radiotherapy enhances the tumor antivascular activity of CA4P in human non-small-cell lung cancer, resulting in sustained tumor vascular shutdown. (c) 2007 Elsevier Inc.