Navigation Links
Second-line CML drugs evoke faster, better front-line remissions

HOUSTON -- Two drugs approved for treatment of drug-resistant chronic myeloid leukemia provide patients with quicker, better responses as a first therapy than the existing front-line medication, according to two studies published online by the New England Journal of Medicine.

Separate international phase III clinical trials compared high-quality remissions after one year of treatment between the standard-of-care drug imatinib, also known as Gleevec, and the second-line drugs nilotinib (Tasigna) and dasatinib (Sprycel). In both trials, previously untreated CML patients who took the newer drugs reached complete cytogenetic response and major molecular response two important measures of remission -- faster than those taking imatinib. They were also less likely to have their disease progress to advanced stages.

"The second-generation CML drugs are more effective than imatinib and less toxic overall," said Hagop Kantarjian, M.D., professor and chair of The University of Texas MD Anderson Cancer Center's Department of Leukemia. Kantarjian is the corresponding author of the dasatinib study and co-author of the nilotinib study.

Drugs likely to increase survival

"We've learned in cancer therapy that it's important to use your big guns up front," Kantarjian said. "We know that achieving complete cytogenetic response or major molecular response within a year of starting treatment is associated with more favorable long-term survival. Using these second-generation drugs first will likely improve outcomes for patients with chronic myeloid leukemia."

Imatinib, a targeted therapy that blocks the activity of a fusion protein called BCR-ABL that is created by the aberrant Philadelphia chromosome, was a breakthrough drug for CML, nearly doubling the median five-year survival rate for the disease from 50 to 90 percent.

However, 30-40 percent of imatinib patients don't reach a complete cytogenetic or major molecular response, and over time their disease becomes resistant to the drug, Kantarjian said.

(Complete cytogenetic response is the absence of the defective chromosome that causes the disease. Major molecular response is defined as a level of .1 percent or lower of the BCR-ABL oncoprotein as measured by a more sensitive test than traditional cytogenetic analysis.)

Dasatinib vs. Imatinib

In the Dasatinib versus Imatinib Study In Treatment-nave CML Patients (DASISION) trial, 519 previously untreated CML patients were randomized to either 100 mg of dasatinib once a day or 400 mg of imatinib once a day.

In the dasatinib arm, 77 percent of patients achieved a confirmed complete cytogenetic response (CCyR), 46 percent reached major molecular response (MMR) and 1.9 percent had their CML progress.

Of those receiving imatinib, 66 percent reached complete cytogenetic response, 28 percent major molecular response, and 3.5 percent had their disease progress.

Responses were faster with dasatinib, with 54 percent at CCyR at 3 months and 73 percent at six months compared with 31 percent and 59 percent for imatinib.

Side effects for dasatinib and imatinib were mostly low-grade. Hematologic side effects were slightly more common on dasatinib, while other low-grade side effects such as nausea, vomiting, muscle pain and inflammation were higher on imatinib.

Nilotinib vs. Imatinib

In the Evaluating Nilotinib Efficacy and Safety in Clinical Trials Newly Diagnosed Patients (ENEST) trial, 836 new CML patients were randomized to either 300 mg or 400 mg of nilotinib twice daily, or to 400 mg of imatinib once a day.

Results in both nilotinib arms of the trial were nearly identical. In the 300 mg twice daily group, 80 percent of patients reached complete cytogenetic response, 44 percent achieved major molecular response and less than 1 percent had disease progression. For the higher dose nilotinib, the numbers were 78 percent, 43 percent and also less than 1 percent.

In the imatinib arm, 65 percent achieved complete cytogenetic response, 22 percent reached major molecular response, and 4 percent had their disease progress.

Patients on nilotinib achieved major molecular response earlier than those on imatinib, with median times to MMR of 5.7 and 5.8 months, compared with 8.3 months for imatinib.

Nilotinib and imatinib had favorable safety profiles, with serious side effects uncommon for either drug. Hematologic side effects decreased levels of red blood cells, white blood cells or platelets -- were slightly more common among those on imatinib. Nausea, diarrhea, vomiting, muscle spasms and edema were higher on imatinib, but rash, headache, hair loss and itching were higher on nilotinib.

Novartis, the company that makes imatinib, also developed nilotinib, and Bristol-Myers Squibb developed dasatinib, both of which are more potent inhibitors of the BCR-ABL protein. The two drugs are approved as second-line therapy after imatinib fails or as first therapy for those who cannot take imatinib. Both companies are expected to seek U.S. Food and Drug Administration approval for the two drugs as initial therapy for CML.

"Findings from both of these studies confirm the single-arm trials done at MD Anderson, which had shown superiority of second-generation drugs in a front-line setting," Kantarjian said. The two ongoing single-arm clinical trials, led by Jorge Cortes, M.D., professor in MD Anderson's Department of Leukemia, compare the performance of the drugs in new patients to historical results from earlier trials of imatinib.


Contact: Scott Merville
University of Texas M. D. Anderson Cancer Center

Related medicine news :

1. Second-line CML drugs evoke faster response than front-line therapy
2. Patient age not a factor in use of second-line therapy for lung cancer
3. Second-line CML drug evokes faster response, fewer side effects, pivotal study finds
4. New Drugs, New Combinations Fight Breast Cancer
5. NICE guidelines ration affordable osteoporosis drugs
6. Bone Drugs May Beat Back Breast Cancer
7. Rehabilitation for Opiate Addiction Without Maintenance Drugs
8. Review and approval of oncology and hematology drugs at FDA from 2005 to 2007
9. Fake Drugs Bought on the Web Pose Big Health Risks
10. Scientists show how molecular switch helps pancreatic cancer beat drugs
11. Common antidepressant drugs linked to lactation difficulties in moms
Post Your Comments:
(Date:6/27/2016)... ... June 27, 2016 , ... ... industry today announced its strategic partnership with Connance, a healthcare industry leader ... two companies’ proven, proprietary technology combine to provide health systems, hospitals and ...
(Date:6/27/2016)... ... ... recently awarded their highest five-star rating to Best Buy Eyeglasses, an ... United States and Canada wear eyeglasses. Once considered to be a purely functional part ... fashion statement. Even celebrities use glasses as a way of creating an iconic image—like ...
(Date:6/26/2016)... ... , ... On June 10-11, 2016, A Forever Recovery, a holistic treatment center ... Breakfast Table in Battle Creek, MI, where the rehabilitation facility is located. This annual ... the world’s leading providers of cereal and other breakfast foods. Its residents often refer ...
(Date:6/26/2016)... ... June 26, 2016 , ... PawPaws brand pet ... product that was developed to enhance the health of felines. The formula is all-natural ... two main herbs in the PawPaws Cat Kidney Support Supplement Soft Chews ...
(Date:6/26/2016)... (PRWEB) , ... June 26, 2016 , ... ... fertility once they have been diagnosed with endometriosis. These women need a treatment ... also require a comprehensive approach that can help for preservation of fertility and ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... June 24, 2016  Global Blood Therapeutics, Inc. (GBT) ... developing novel therapeutics for the treatment of grievous ... the closing of its previously announced underwritten public ... the public offering price of $18.75 per share. ... offered by GBT. GBT estimates net proceeds from ...
(Date:6/24/2016)... 24, 2016 The Academy of Managed Care ... that would allow biopharmaceutical companies to more easily ... make formulary and coverage decisions, a move that addresses ... medicines. The recommendations address restrictions in the ... the drug label, a prohibition that hinders decision makers ...
(Date:6/24/2016)... PUNE, India , June 24, 2016 ... "Pen Needles Market by Type (Standard Pen Needles, Safety ... 12mm), Therapy (Insulin, GLP-1, Growth Hormone), Mode of Purchase ... published by MarketsandMarkets, This report studies the market for ... is expected to reach USD 2.81 Billion by 2021 ...
Breaking Medicine Technology: