Literature Scan
Continued from page 40
tumor samples from 96 patients with acute
myeloid leukemia (AML), 51 patients with
acute lymphocytic leukemia (ALL), and 38
patients with myeloproliferative neoplasms.
Of the tumors studied, two samples
– one from a pediatric patient with B-cell
ALL and another from an adult patient
with AML – each had one ALK mutation.
The researchers then introduced the two
mutations into laboratory-grown leukemia
cells that normally depend on an external
growth factor for survival. They found that
the mutations allowed the cells to grow,
despite the absence of an external growth factor, thus indicating that these mutations were
capable of driving abnormal cell growth.
Additional laboratory studies indicated that leukemia cells harboring either
of the two established mutations could
be inhibited by several ALK inhibitors,
including crizotinib and ceritinib, both of
which are approved by the U.S. Food and
Drug Administration for the treatment of
ALK-positive metastatic non-small cell
lung cancer.
“Genome sequencing is revealing a vast
mutational landscape in leukemia, offering new opportunities for treatment with
targeted therapy,” the authors concluded.
“We propose that tumors harboring ALK
mutations may be therapeutically tractable
for personalized treatment of certain aggressive leukemias with ALK inhibitors.”
TASIGNA® (nilotinib) Capsules for oral use
Initial U.S. Approval: 2007
BRIEF SUMMARY: Please see package insert for full prescribing
information.
WARNING: QT PROLONGATION AND SUDDEN DEATHS
• Tasigna prolongs the QT interval. Prior to Tasigna administration and
periodically, monitor for hypokalemia or hypomagnesemia and correct
deficiencies (5.2). Obtain ECGs to monitor the QTc at baseline, seven
days after initiation, and periodically thereafter, and following any
dose adjustments (5.2, 5.3, 5.7, 5.15).
• Sudden deaths have been reported in patients receiving nilotinib (5.3).
Do not administer Tasigna to patients with hypokalemia, hypomagnesemia, or long QT syndrome (4, 5.2).
• Avoid use of concomitant drugs known to prolong the QT interval and
strong CYP3A4 inhibitors (5.8).
• Avoid food 2 hours before and 1 hour after taking the dose (5.9).
1 INDICATIONS AND USAGE
1.1 Newly Diagnosed Ph+ CML-CP
Tasigna (nilotinib) is indicated for the treatment of adult patients with
newly diagnosed Philadelphia chromosome positive chronic myeloid
leukemia (Ph+ CML) in chronic phase. The effectiveness of Tasigna is
based on major molecular response and cytogenetic response rates [see
Clinical Studies (14.1) in the full prescribing information].
1.2 Resistant or Intolerant Ph+ CML-CP and CML-AP
Tasigna is indicated for the treatment of chronic phase and accelerated
phase Philadelphia chromosome positive chronic myelogenous leukemia
(Ph+ CML) in adult patients resistant or intolerant to prior therapy that
included imatinib. The effectiveness of Tasigna is based on hematologic
and cytogenetic response rates [see Clinical Studies (14.2) in the full
prescribing information].
4 CONTRAINDICATIONS
Do not use in patients with hypokalemia, hypomagnesemia, or long
QT syndrome [see Boxed Warning].
5 WARNINGS AND PRECAUTIONS
5.1 Myelosuppression
Treatment with Tasigna can cause Grade 3/4 thrombocytopenia, neutropenia and anemia. Perform complete blood counts every 2 weeks for the first
2 months and then monthly thereafter, or as clinically indicated. Myelosuppression was generally reversible and usually managed by withholding
Tasigna temporarily or dose reduction [see Dosage and Administration
(2.2) in the full prescribing information].
5.2 QT Prolongation
Tasigna has been shown to prolong cardiac ventricular repolarization as
measured by the QT interval on the surface ECG in a concentrationdependent manner [see Adverse Reactions (6.1), Clinical Pharmacology
(12.6) in the full prescribing information]. Prolongation of the QT interval can result in a type of ventricular tachycardia called torsade de
pointes, which may result in syncope, seizure, and/or death. ECGs
should be performed at baseline, 7 days after initiation of Tasigna, and
periodically as clinically indicated and following dose adjustments [see
Warnings and Precautions (5.15)].
Tasigna should not be used in patients who have hypokalemia, hypomagnesemia or long QT syndrome. Before initiating Tasigna and periodically, test electrolyte, calcium and magnesium blood levels. Hypokalemia
or hypomagnesemia must be corrected prior to initiating Tasigna and
these electrolytes should be monitored periodically during therapy [see
Warnings and Precautions (5.15)].
Significant prolongation of the QT interval may occur when Tasigna is
inappropriately taken with food and/or strong CYP3A4 inhibitors and/or
medicinal products with a known potential to prolong QT. Therefore,
coadministration with food must be avoided and concomitant use with
strong CYP3A4 inhibitors and/or medicinal products with a known potential to prolong QT should be avoided [see Warnings and Precautions (5.8,
5.9)]. The presence of hypokalemia and hypomagnesemia may further
prolong the QT interval [see Warnings and Precautions (5.7, 5.15)].
5.3 Sudden Deaths
Sudden deaths have been reported in 0.3% of patients with CML treated
with nilotinib