Biomedical Engineering Reference
In-Depth Information
6.4 months. In the CP patients, CHR was achieved in 26 patients and
maintained in 8 patients (8 patients entered the study in CHR) for
an overall CHR rate of 85%; the median duration of CHR was 7.7+
months. Overall CyR was achieved in 27.5% and the median dura-
tion of MCyR was 6+ months. The MMR was achieved in 15% of pa-
tients. Interestingly a reduction of baseline T315I mutated clone oc-
curred in 56.7% of CP. Toxicity: Grade 3/4 related events occurred
in 45 of 66 (68%) patients. The most commonly reported events
were thrombocytopenia (58%), anemia (36%) and neutropenia
(33%). Grade 3/4 non-hematologic toxicities were uncommon with
no events occurring in >5% of patients and infection (3%) the most
common event. Treatment delays occurred in approximately 50%
of the patients with median duration of approximately 12 days for
all disease phases and cycles (CP=12, AP=10, and BP=12 days). The
safety data from two long-term phase II studies of omacetaxine in
170 patients with CML in the CP, AP, or BP who were resistant to
intolerant of TKIs were reported. Grade 3 or 4 thrombocytopenia,
neutropenia, and anemia occurred in 49%, 34% and 30% of the 170
patients, respectively.
8.7
Conclusions and Future Directions
Imatinib has been the standard therapy for CML for the past decade
due to its remarkable activity and mild toxicity. Despite the high
response rate, imatinib has not been proven as a curative option for
the CML patients. The second generation TKIs such as nilotinib and
dasatinib are effective in imatinib-resistant and -intolerant patients.
Based on the data from DASISION trial and ENESTnd trials,
dasatinib and nilotinib were recommended for the first-line
treatment of CML. There were no head to head trial comparing the
efficacy of nilotinib and dasatinib. However there are some concerns
about the side effect profiles of both drugs. In the dasatinib groups
there were mildly increased incidence of pleural effusion and have
more CML related deaths than the imatinib group. In the nilotinib
group there have been increased lipase, liver enzymes, and glucose
levels. QTc prolongation from nilotinib creates concerns about the
toxicity in the long-term use. Allogeneic HSCT is an alternative
option for patients who progressed to BP or patients with T315I
mutations. Ponatinib (AP24534) showed promising results against
T315I mutation and F317L mutations in early studies.
