Dasatinib and nilotinib

[Guest guest]

New Therapeutic Options in CML and What They Mean for Patients: An Expert

Interview With Dr. Cortes (Posted 01/28/2008)

Medscape: Dasatinib and nilotinib have recently been approved for use in

patients with CML who develop resistance to or are refractory to imatinib. How

would you summarize the preliminary de novo data on dasatinib? Dr. Cortes:

Although we are very pleased with the overall results achieved with imatinib in

patients with CML, a subset of patients do not respond as well as we would like.

We now have 2 drugs that are more potent than imatinib and that are effective

when imatinib fails. If we can use them in front-line therapy and achieve

responses in the few patients who do not respond to imatinib -- perhaps

attaining early responses that correlate with better long-term outcomes -- then

we can further improve long-term event-free survival and overall survival for

all patients.

The study with nilotinib had an identical design to the dasatinib study, but all

study participants received the approved dose of 400 mg twice daily. Other than

that, all study parameters were the same as the dasatinib trial. Although these

studies were not comparative, patient characteristics are also alike between the

2 studies.

I would advise community oncologists to make every possible effort to include

their patients in the current trials. What we need to do is find the best

treatment possible for our patients. The only way that we are going to be able

to accomplish that is to enroll them in trials that will help us answer the

questions we have about these new agents.

http://www.medscape.com/viewarticle/568343

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Medscape: Precisely what is the role of SRC in CML? Is it a relevant new target,

or is BCR-ABL still the main target? Dr. Druker: It is absolutely clear that

the main target in CML is BCR-ABL: regardless of whether somebody is newly

diagnosed or somebody has relapsed on imatinib therapy, BCR-ABL still remains

the primary target. There may be a small percentage of patients who become

imatinib-resistant, whose disease becomes BCR-ABL-independent.

Medscape: How do you see treatment for CML evolving in the near future? Dr.

Druker: We will continue to see rapid evolution in the therapy of CML. It's

absolutely clear that achieving a major molecular response at 1 year correlates

with progression-free survival, and it is likely that the goal of therapy will

become maximizing the numbers of patients who achieve that landmark. Over the

coming years and decade, I would like to see us move toward shorter treatments

that can be curative. http://www.medscape.com/viewarticle/520562.

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July 17, 2008 - Imatinib has proven to be a highly effective first-line therapy

for newly diagnosed patients with BCR-ABL-positive chronic myeloid leukemia

(CML) in the chronic phase. However, for approximately one third of patients,

standard-dose imatinib is not effective. In the July 10 issue of the Journal of

Clinical Oncology, researchers found that at 5 years, the cumulative incidence

of complete cytogenetic response (CCyR) to standard-dose imatinib was 82.7% and

of major molecular response was 50.1%. Estimated overall survival was 83.2% and

progression-free survival was 82.7%. At 5 years, 25% of patients had

discontinued treatment because of a lack of response and/or toxicity. The

probability, at 5 years, of patients remaining in major cytogenetic response

while still taking imatinib was 62.7%. Dr. Cortes notes that interferon,

cytarabine, and other agents with known clinical activity in CML or that

interfere with other pathways involved in CML have been found to be synergistic

with imatinib, although initial attempts at combination therapies have not been

met with much success. More can be found here:

http://www.medscape.com/viewarticle/577662

A few little tidbits for you to ponder over,

Lottie