Two drugs approved for treatment of drug-resistant chronic myeloid leukemia ( CML ) provide patients with quicker, better responses as a first therapy than the existing front-line medication.

These two studies are published in 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 ( Glivec in Europe ), 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 faster than those taking Imatinib. They were also less likely to have their disease progress to advanced stages.

According to Hagop Kantarjian, at The University of Texas MD Anderson Cancer, the second-generation CML drugs are more effective than Imatinib and less toxic overall.

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.

Dasatinib versus Imatinib

In the DASISION ( Dasatinib versus Imatinib Study In Treatment-naïve CML Patients ) 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% of patients achieved a confirmed complete cytogenetic response ( CcyR ), 46% reached major molecular response ( MMR ) and 1.9% had their chronic myeloid leukemia progress.

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

Responses were faster with Dasatinib, with 54% at CCyR at 3 months and 73% at six months compared with 31% and 59% 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 versus Imatinib

In the ENEST ( Evaluating Nilotinib Efficacy and Safety in Clinical Trials - Newly Diagnosed Patients ) 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% of patients reached complete cytogenetic response, 44% achieved major molecular response and less than 1% had disease progression. For the higher dose nilotinib, the numbers were 78%, 43% and also less than 1%.

In the Imatinib arm, 65% achieved complete cytogenetic response, 22% reached major molecular response, and 4% 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.

Source: University of Texas MD Anderson Cancer Center, 2010

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