Safety and Pharmacokinetics of Motesanib in Combination with Panitumumab and Gemcitabine-Cisplatin in Patients with Advanced Cancer
Table 4
Mean concentrations of gemcitabine, platinum, and panitumumab.
Motesanib dose cohort
No motesanib (0 mg QD)
50 mg QD
75 mg QD
100 mg QD
125 mg QD
75 mg BID
Plasma gemcitabine concentration (cycle 1)
8
8
6
6
11
2
Mean, ng/mL (SD)
11000 (4220)
8450 (7310)
14400 (6020)
6160 (3690)
16100 (6800)
8290 (NR)
Plasma platinum concentration (cycle 1)
8
8
6
6
11
1
Mean total platinum, ng/mL (SD)
3580 (273)
2960 (730)
3630 (399)
3330 (536)
3560 (524)
3920 (NR)
Mean free platinum, ng/mL (SD)
2190 (283)
1420 (924)
2250 (584)
1550 (321)
2140 (469)
2650 (NR)
Serum panitumumab concentration
Cycle 1
8
7
6
5
11
2
Postdose mean concentration, g/mL (SD)
206 (76.4)
174 (24.9)
158 (24.2)
194 (27.1)
203 (82.9)
189 (NR)
Cycle 2
6
7
6
5
6
1
Predose mean concentration, g/mL (SD)
11.2 (15.5)
9.0 (5.8)
13.1 (13.5)
18.9 (10.7)
13.4 (14.2)
11.2 (NR)
6
5
6
4
6
1
Postdose mean concentration, g/mL (SD)
186 (62.9)
193 (37.5)
194 (21.5)
224 (51.8)
213 (39.0)
217 (NR)
Cycle 4
4
3
5
4
3
0
Predose mean concentration, g/mL (SD)
56.5 (39.6)
10.5 (6.4)
32.5 (21.3)
41.6 (16.5)
21.7 (22.0)
NR
3
3
6
2
3
0
Postdose mean concentration, g/mL (SD)
275 (118)
232 (52.8)
218 (26.1)
290 (NR)
170 (55.0)
NR
BID: twice daily; NR: not reported; QD: once daily. Mean free platinum concentrations are based on an assessment of platinum concentrations in plasma ultrafiltrate.
