Statin as a therapeutic agent in gastroenterological cancer

Table 1 Randomized controlled trials of combination therapy with statins

Cancer type	Study type	Statin (dose)	Combination therapies	Outcome
Gastric cancer	Phase III	Simvastatin (40 mg/d)	Capecitabine andcisplatin	Simvastatin + capecitabine-cisplatin did not increase progression-free survival compared with capecitabine-cisplatin alone
	Phase II	Pravastatin (40 mg/d)	Epirubicin, cisplatinand capecitabine	Pravastatin + standard chemotherapy was well tolerated, but did not improve progression-free survival at 6 months compared with chemotherapy alone
Colorectal	Phase III	Simvastatin (40 mg/d)	FOLFIRI/XELIRI	Simvastatin + FOLFIRI/XELIRI did not increase progression-free survival compared with FOLFIRI/XELIRI alone
Hepatocellular	Phase III	Pravastatin (40 mg/d)	Sorafenib	Pravastatin + sorafenib did not improve overall or progression-free survival compared with sorafenib alone
	Phase II	Pravastatin (40 mg/d)	Transcatheter arterialembolization followedby fluorouracil	Pravastatin + standard therapy prolonged overall survival compared with standard therapy alone
Pancreatic	Phase II	Simvastatin (40 mg/d)	Gemcitabine	Simvastatin + gemcitabine was well tolerated, but did not decrease time to progression compared with gemcitabine alone

Table 2 Properties of statins

Statin	Solubility[3]	Metabolism[3]	Human dose to lower cholesterol (mg)
			Low	Moderate	High
Simvastatin	Lipophilic	CYP3A4	10	20-40	-
Atorvastatin	Lipophilic	CYP3A4/2C9	-	10-20	40-80
Fluvastatin	Lipophilic	CYP2C9	20-40	80	-
Pitavastatin	Lipophilic	Non-CYP450	-	1-4	-
Lovastatin	Lipophilic	CYP3A4/2C9	20	40-80	-
Rosuvastatin	Hydrophilic	Non-CYP450	-	5-10	20-40
Pravastatin	Hydrophilic	Non-CYP450	10-20	40-80	-