Oral nelfinavir before and during radiation therapy for rectal cancer: Changes in tumor perfusion and correlation between tissue and radiological markers of response.

491 Background: Nelfinavir, an inhibitor of AKT in the PI3-kinase pathway, is a radiosensitizer which increases tumor blood flow and reduces hypoxia in preclinical models. We conducted a pilot study of nelfinavir before and during hypofractionated pelvic radiotherapy (RT) in patients with rectal cancer to evaluate the safety of the combination, changes in tumor perfusion and a tissue biomarker of radiosensitization, tumor cell density (TCD). Methods: Eight patients with T3-4 N1-2 M1 rectal cancer received 7 days of oral nelfinavir (1250 mg bd) and a further 7 days of nelfinavir during pelvic RT (25 Gy/5 fractions/7 days). Safety was evaluated by CTCAE v 4.0. Dynamic contrast enhanced (DCE) CT and MRI scans were performed pre-treatment, after 7 days nelfinavir and prior to last fraction of RT. TCD was performed in biopsies taken pre-treatment and 7 days post-radiotherapy (West N et al. Br J Cancer. 2010, 102; 1519-23). Radiological response and tumor regression grade (TRG) was assessed on MRI 8 weeks from ...