Metformin Reduce the Relapse Rate on Patients With B-cell Precursor (Ph+ Negative) Acute Lymphoblastic Leukemia

Summary

Metformin's Antitumor activity were identified from differens diabetic patients trials, mainly associated to its mechanism of action and protein - kinase AMPK (AMP-activated protein kinase) activation. According to Cancer and Diabetes International Consensus from 2012, diabetes increases the risk for developping cancer and metformin has an protector effect against cancer cells and has an impact on overall survival. Chemotherapy drug resistance induces treatment fail in oncology. Metformin increases AMPK levels, blocks PI3K (phosphatidylinositol 3- kinase)/ AKT /mTOR(mammailian Target of Rapamycin) pathway but few evidence associated with drug resistance gene expression. This is an, experimental one-center study that pretends to stablish the effect of adding metformin 850 mg PO three times a day over the multi-drug resistance gene expression (ABCB1) in de novo Acute Lymphoblastic Leukemia in one 7-days cycle with prednisone as pre-treatment- and on the induction remission treatment.

Timeline

Start

2015-01-01

Primary completion

2016-12-01

Completion

2017-04-30

Publications

• Background Kim HG, Hien TT, Han EH, Hwang YP, Choi JH, Kang KW, Kwon KI, Kim BH, Kim SK, Song GY, Jeong TC, Jeong HG. Metformin inhibits P-glycoprotein expression via the NF-kappaB pathway and CRE transcriptional activity through AMPK activation. Br J Pharmacol. 2011 Mar;162(5):1096-108. doi: 10.1111/j.1476-5381.2010.01101.x.
• Background Olarte Carrillo I, Ramos Penafiel C, Miranda Peralta E, Rozen Fuller E, Kassack Ipina JJ, Centeno Cruz F, Garrido Guerrero E, Collazo Jaloma J, Nacho Vargas K, Martinez Tovar A. Clinical significance of the ABCB1 and ABCG2 gene expression levels in acute lymphoblastic leukemia. Hematology. 2017 Jun;22(5):286-291. doi: 10.1080/10245332.2016.1265780. Epub 2016 Dec 14.
• Ramos-Penafiel C, Olarte-Carrillo I, Ceron-Maldonado R, Rozen-Fuller E, Kassack-Ipina JJ, Melendez-Mier G, Collazo-Jaloma J, Martinez-Tovar A. Effect of metformin on the survival of patients with ALL who express high levels of the ABCB1 drug resistance gene. J Transl Med. 2018 Sep 3;16(1):245. doi: 10.1186/s12967-018-1620-6.

Drugs

Indications