Table 1.

Antitumor activity of PX-478 in combination with radiation and chemotherapy in pancreatic tumors

Tumor size mm3TreatmentDose mg/kgRoute scheduleLog cell killRegression %T/C %
CF-PAC-1200PX-47810p.o. qd ×51.3115.332.5*
PX-478203.8738.210.8*
Radiation 1 Gy qd ×5 and FU 20 mg/kg i.v. qd ×5
Alone0.45065.3*
PX-47810p.o. qd ×53.9063.66.5*
PX-47820p.o. qd ×5Lethal
SU.86.86600PX-4784p.o. qd ×50.56032.1*
PX-47881.01016.8*
Radiation 1 Gy qd ×5 and FU 20 mg/kg i.v. qd ×5
Alone0.47038.7*
PX-4784p.o. qd ×51.21016.1*
PX-4788p.o. qd ×5>1.6566.73.0*
Panc-1125PX-4785p.o. qd ×53.30054.0
PX-47810p.o. qd ×53.47036.7
PX-47820p.o. qd ×55.2072.09.8*
Radiation 1 Gy qd ×5 and gemcitabine 120 mg/kg i.p. q3d ×3
Alone0.52035.8
PX-4785p.o. qd ×54.1635.613.0*
PX-47810p.o. qd ×54.5171.810.6*
PX-47820p.o. qd ×56.9479.07.6*
SU.86.86400PX-4785p.o. qd ×50.46060.9
PX-47810p.o. qd ×50.74048.9*
PX-47820p.o. qd ×51.1111.728.7*
Radiation 1 Gy qd ×5 and gemcitabine 120 mg/kg i.p. q3d ×3
Alone1.8424.624.5*
PX-4785p.o. qd ×51.8420.625.8*
PX-47810p.o. qd ×52.454019.6*
PX-47820p.o. qd ×52.45>75.815.8*

NOTE: Female SCID mice with s.c. pancreatic tumors with a mean tumor volume as shown at the start of treatment were administered radiation and chemotherapy with or without PX-478. Antitumor responses expressed as log cell kill, regression or test over control (T/C) were calculated compared with a vehicle-alone-treated control. There were 8 mice in each treatment group.

Abbreviations: p.o., orally; qd ×5, once a day for 5 days; q3d ×3, every 3 days for a total of 3 doses.

  • *P < 0.01 compared with control values (Mann-Whitney test).

  • FU given 1 hour and PX-478 4 hours before radiation.

  • PX-478 given 4 hours before radiation and gemcitabine on days 12, 15, and 17.