Featured Research

from universities, journals, and other organizations

Combination therapy with midostaurin improves survival of acute myeloid leukemia patients with FLT3 mutations, phase 1

Date:
December 21, 2009
Source:
Dana-Farber Cancer Institute
Summary:
A targeted drug that is active against acute myeloid leukemia is particularly effective when teamed with chemotherapy in patients whose cancer cells harbor a key genetic mutation, according to new research.

A targeted drug that is active against acute myeloid leukemia (AML) is particularly effective when teamed with chemotherapy in patients whose cancer cells harbor a key genetic mutation, researchers at Dana-Farber Cancer Institute and their colleagues will report at the American Society of Hematology's (ASH) annual meeting on Dec. 7.

The Phase I study focused on the potential of administering the drug midostaurin (PK412) with high doses of the chemotherapy drug cytarabine in AML patients whose disease has been driven into remission by cytarabine and another chemotherapy agent, daunorubicin. Midostaurin is a kinase inhibitor, blocking a key class of enzymes -- kinases -- that often spur cancer cell growth. It works by targeting the FLT3 cell receptor, which is overactive in the white blood cells of many AML patients as a result of genetic mutation.

On its own, midostaurin reduces the number of circulating leukemia cells in AML patients, but rarely produces complete remissions. Preclinical studies have shown that FLT3 inhibitors like midostaurin work synergistically with chemotherapy agents, reinforcing each other's effect against cancer.

In the new study, researchers led by Richard Stone, MD, of Dana-Farber treated 40 newly diagnosed AML patients under age 61 with daunorubicin and cytarabine to induce remission, followed by high-dose cytarabine and oral midostaurin in twice-daily doses of either 100 mg or 50 mg. The higher dose level often produced nausea and vomiting, but patients at the lower dosage tolerated the therapy well.

Of the 40 patients who completed the therapy, 32 (or 80 percent of the group) had a complete response, in which circulating AML cells were reduced to undetectable levels. Complete responses occurred in 74 percent of the patients whose cells had normal FLT3, and in 92 percent of those with mutated FLT3 -- significantly better than had been achieved with midostaurin alone. Eighty-five percent of the group with mutated FLT3 were alive one year after treatment, and 62 percent were alive two years after. These results were comparable to those of the normal FLT3 group (81 percent one-year survival, and 62 percent two-year survival).

Although the study involved a relatively small number of patients, "the results suggest that a combination of an FLT3 inhibitor and chemotherapy might be effective enough to reduce the need for donor stem cell transplantation in AML patients with mutated FLT3 who have entered first remission," Stone says. "These findings also support the value of ongoing phase 3 studies of the potential benefits of midostaurin during various phases of AML treatment."

The study's senior author is Frank Giles, MD, of the Institute for Drug Development, in San Antonio, Texas. Co-authors include: Thomas Fisher, MD, of University Hospital, in Magdeburg, Germany; Ronald Paquette, MD, of Ronald Reagan UCLA Medical Center; Gary Schiller, MD, of UCLA School of Medicine; Charles Schiffer, MD, of the Barbara Ann Karmanos Cancer Center, in Detroit; Gerhard Ehninger, MD, of University Hospital, in Dresden, Germany; Jorge Cortes, MD, and Hagop Kantarjian, MD, of the University of Texas M.D. Anderson Cancer Center; Daniel DeAngelo, MD, PhD, of Dana-Farber; and Alice Huntsman-Labed, Catherine Dutreix, MD, and Sumita Rai, MD, of Novartis Oncology.

The authors are supported by research funding from: Novartis AG, Cephalon, Inc., Millenium Pharmaceuticals, Genzyme Corp., Vion Corp. Centocor Ortho Biotech Inc., Eli Lilly and Co., Bristol-Myers Squibb, Pfizer Inc., Enzon Pharmaceuticals, Celgene Corp., and Merck & Co.


Story Source:

The above story is based on materials provided by Dana-Farber Cancer Institute. Note: Materials may be edited for content and length.


Cite This Page:

Dana-Farber Cancer Institute. "Combination therapy with midostaurin improves survival of acute myeloid leukemia patients with FLT3 mutations, phase 1." ScienceDaily. ScienceDaily, 21 December 2009. <www.sciencedaily.com/releases/2009/12/091207181420.htm>.
Dana-Farber Cancer Institute. (2009, December 21). Combination therapy with midostaurin improves survival of acute myeloid leukemia patients with FLT3 mutations, phase 1. ScienceDaily. Retrieved October 1, 2014 from www.sciencedaily.com/releases/2009/12/091207181420.htm
Dana-Farber Cancer Institute. "Combination therapy with midostaurin improves survival of acute myeloid leukemia patients with FLT3 mutations, phase 1." ScienceDaily. www.sciencedaily.com/releases/2009/12/091207181420.htm (accessed October 1, 2014).

Share This



More Health & Medicine News

Wednesday, October 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Some Positive Ebola News: Outbreak 'Contained' In Nigeria

Some Positive Ebola News: Outbreak 'Contained' In Nigeria

Newsy (Sep. 30, 2014) The CDC says a new case of Ebola has not been reported in Nigeria for more than 21 days, leading to hopes the outbreak might be nearing its end. Video provided by Newsy
Powered by NewsLook.com
UN Ebola Mission Head: Immediate Action Is Crucial

UN Ebola Mission Head: Immediate Action Is Crucial

AFP (Sep. 30, 2014) The newly appointed head of the United Nations Mission for Ebola Emergency Response (UNMEER), Anthony Banbury, outlines operations to tackle the virus. Duration: 00:39 Video provided by AFP
Powered by NewsLook.com
CDC Confirms First Case of Ebola in US

CDC Confirms First Case of Ebola in US

AP (Sep. 30, 2014) The CDC has confirmed the first diagnosed case of Ebola in the United States. The patient is being treated at a Dallas hospital after traveling earlier this month from Liberia. (Sept. 30) Video provided by AP
Powered by NewsLook.com
New Breast Cancer Drug Extends Lives In Clinical Trial

New Breast Cancer Drug Extends Lives In Clinical Trial

Newsy (Sep. 30, 2014) In a clinical trial, breast cancer patients lived an average of 15 months longer when they received new drug Perjeta along with Herceptin. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins