About My Health Careers Internship MedBlogs Contact us
Medindia LOGIN REGISTER
Advertisement

Research: AKT Inhibitor AZD5363 Well Tolerated, Yielded Partial Response in Patients With Advanced Solid Tumors

by Rukmani Krishna on April 8, 2013 at 11:57 PM
Font : A-A+

Research: AKT Inhibitor AZD5363 Well Tolerated, Yielded Partial Response in Patients With Advanced Solid Tumors

The investigational drug AZD5363, which has shown activity in preclinical studies, was well tolerated in humans, and two patients with advanced solid tumors showed partial response. The data will be presented at the AACR Annual Meeting 2013, held in Washington, D.C., April 6-10.

"PI3K/AKT signaling is very important in cancer cells," said Udai Banerji, M.D., Ph.D., clinical senior lecturer at the Institute of Cancer Research and The Royal Marsden NHS Foundation Trust in London, United Kingdom. "This signaling pathway is highjacked by abnormalities or mutations in genes that can cause a normal cell to behave like a cancer cell."

Advertisement

AZD5363 is a new-generation drug inhibiting the three forms of the AKT protein: AKT1, AKT2 and AKT3. It has shown promising results in several tumor cell lines and animal studies. In prior clinical trials, AKT inhibitors have almost always been tested in continuous dosing schedules, resulting in excessive toxicity, according to Banerji.

Banerji and colleagues conducted two phase I studies and administered AZD5363 to the patients in two schedules: continuous dosing seven days a week and intermittent dosing with four days on and three days off.
Advertisement

Among the 92 patients recruited thus far, an intermittent dosing schedule of 480 mg twice a day was generally well tolerated. Side effects included high blood sugar, rash and diarrhea. "But what is important about these side effects, such as raised blood sugar, is that these are known consequences of targeting the AKT pathway," said Banerji. "This provides proof of principle that the drug is working."

Using pharmacokinetics studies, the team determined that the dose achieved in the patients blood was comparable to the dose used in preclinical studies in which they saw positive outcomes. More than 30 percent reduction was seen in the levels of two proteins, pPRAS40 and pGSK3 beta, in plucked hair and blood samples collected from the patients, suggesting that the drug successfully inhibited AKT.

One patient with ovarian cancer and one with cervical cancer showed partial response to treatment. Both had a mutation in either AKT1 or PIK3CA in their cancers. A third patient with ovarian cancer with a PIK3CA mutation had prolonged stable disease.

"What is very gratifying is that a response like this to a single agent is not something we see very often," said Banerji. "Also, these data support the growing realization that AKT inhibitors are beneficial when administered intermittently and not continuously."

Encouraged by these results, AstraZeneca recently initiated two phase Ib studies with patients with prostate and breast cancers. AZD5363 was discovered by AstraZeneca subsequent to collaboration with Astex Therapeutics and its collaboration with The Institute of Cancer Research.

Source: Newswise
Advertisement

Advertisement
News A-Z
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
News Category
What's New on Medindia
Contraceptive Pills in Polycystic Ovary Syndrome (PCOS) Curtail Type 2 Diabetes Risk
Mushroom May Help Cut Down the Odds of Developing Depression
How to Battle Boredom during COVID
View all

Medindia Newsletters Subscribe to our Free Newsletters!
Terms & Conditions and Privacy Policy.


Recommended Reading
Carcinoid Tumors
Carcinoid tumors is a benign tumor that results in carcinoid syndrome. Only 8 to 10% of all ......
Patients With Incurable Solid Tumors and BRCA Mutations Respond to Novel Drug Combination
Anti-cancer activity is being shown in patients with a novel combination of two drugs, who had ......
Genetic Key to Preventing Spine Tumors Found By Researchers in Manchester
Genetic medicine experts have identified a new gene responsible for causing an inherited form of ......
Multiple Myeloma
Multiple Myeloma caught public attention when model turned actress Lisa Ray, who worked in Deepa ......

Disclaimer - All information and content on this site are for information and educational purposes only. The information should not be used for either diagnosis or treatment or both for any health related problem or disease. Always seek the advice of a qualified physician for medical diagnosis and treatment. Full Disclaimer

© All Rights Reserved 1997 - 2021

This site uses cookies to deliver our services. By using our site, you acknowledge that you have read and understand our Cookie Policy, Privacy Policy, and our Terms of Use