COMBINATION THERAPY WITH SYNTHETIC TRITERPENOIDS AND GEMCITABINE
The present invention concerns methods for treating cancer, such as pancreatic cancer, using combination therapies, including the combination of a synthetic triterpenoid, e.g., CDDO-Me, and gemcitabine.
1 . A method for treating a cancer from a group consisting of pancreatic cancer, lung cancer and ovarian cancer, in a mammalian subject, comprising administering to said subject:
a) a compound having the structure:
wherein Y is hydroxy, amino, or a heteroatom-substituted or heteroatom-unsubstituted C 1 -C 3 -alkoxy or C 1 -C 3 -alkylamino; or
a pharmaceutically acceptable salt or hydrate thereof; and
b) gemcitabine;
wherein the combination is effective to treat the cancer.
2 . The method of claim 1 , wherein the cancer is stage IV pancreatic cancer.
3 . The method of claim 2 , wherein the treatment results in an objective reduction of lesion size.
4 . The method of claim 3 , wherein the objective reduction of lesion size is from about 10% to about 100%.
5 . The method of claim 4 , wherein the objective reduction of lesion size is from about 15% to about 50%.
6 . The method of claim 5 , wherein the objective reduction of lesion size is from about 20% to about 35%.
7 . The method of claim 2 , wherein the treatment results in the formation of no new metastases.
8 . The method of claim 2 , wherein the treatment results in an increased white blood cell count in the subject.
9 . The method of claim 2 , wherein the treatment results in an increased platelet count in the subject.
10 . The method of claim 1 , wherein Y is a heteroatom-unsubstituted C 1 -C 2 -alkoxy.
11 . The method of claim 10 , wherein the compound is CDDO-Me.
12 . The method of claim 11 , wherein the compound is provided in a daily dose from about 100 mg to about 600 mg.
13 . The method of claim 12 , wherein the daily dose is from about 150 to about 400 mg.
14 . The method of claim 13 , wherein the daily dose is about 150 mg.
15 . The method of claim 13 , wherein the daily dose is about 300 mg.
16 . The method of claim 11 , wherein the compound is Form A of CDDO-Me.
17 . The method of claim 11 , wherein the compound is Form B of CDDO-Me.
18 . The method of claim 11 , wherein the compound is an amorphous form of CDDO-Me.
19 . The method of claim 18 , wherein the compound is a glassy solid form of CDDO-Me, having an x-ray powder diffraction pattern with a halo peak at approximately 13.5° 2θ, as shown in FIG. 3C , and a T g .
20 . The method of claim 1 , wherein the amount of gemcitabine administered is the maximum tolerated dose (MTD).
21 . The method of claim 1 , wherein the amount of gemcitabine administered is from about 10% to about 90% of the maximum tolerated dose (MTD).
22 . The method of claim 21 , wherein the amount of gemcitabine administered is from about 25% to about 75% of the maximum tolerated dose (MTD).
23 . The method of claim 23 , wherein the amount of gemcitabine administered is about 50% of the maximum tolerated dose (MTD).
24 . The method of claim 1 , wherein the mammalian subject is a primate.
25 . The method of claim 24 , wherein the primate is a human.
26 . The method of claim 1 , wherein the mammalian subject is a cow, horse, dog, cat, pig, mouse, rat or guinea pig.