Figure 6.

Combination therapy with PHA-739358 and sorafenib. (A) Vehicle-treated control tumors grew rapidly, and mice were killed on day 12 after initiation of treatment because of disabling tumor burden in some animals (n = 7). PHA-739358 at a reduced dosage of 15 mg/kg per day (n = 8) and sorafenib at a dosage of 10 mg/kg per day (n = 7) decelerated tumor growth. Combination therapy with PHA-739358 and sorafenib (n = 9) led to complete growth arrest. After cessation of combination therapy (arrow), some tumors began to grow at a very slow rate (see Table 1 and text for statistical data). (B) The same experimental setting as in panel A was used, and the growth arrest of tumors under combination therapy was confirmed (n = 9 in all treatment groups). However, sorafenib monotherapy was stopped on day 8 when tumors quadrupled their size (arrow). Replacement of therapy with PHA-739358 at the standard monotherapy dosage of 15 mg/kg twice per day from day 8 (striped boxes) until the end of the experiment induced shrinkage of tumors (see text). All values are presented as mean +SD.