Biomedical Engineering Reference
In-Depth Information
use of imatinib at higher dose. Hypothyroidism has been reported
with imatinib use and thyroid functions should also be monitored.
Of additional note, imatinib may cause alteration in liver function
tests. Severe hepatotoxicity has been observed in a patient with CML
in blast crisis that was using large doses of acetaminophen during
imatinib therapy and therefore concomitant use of acetaminophen
should be avoided [98]. There is a 5% risk of gastrointestinal bleeding
in patients with large bulky tumors. Therefore it is recommended
that the hemoglobin should be monitored particularly in the first 2
months of imatinib therapy [99].
Karkela published a report describing cardiotoxicity in 10
patients receiving imatinib [100]. In the aforementioned EORTC
62005 study there was no increased cardiac event observed in the
patient population treated for a median time of 24 months. In the
adjuvant American College of Surgeons Oncology Group (ACOSOG)
Z9001 trial, imatinib use was not associated with increased
cardiotoxicity [101]. Although cardiotoxicity is uncommon, patients
who are being considered for imatinib therapy should be informed
of the potential risk of cardiotoxicity. Appropriate diagnostic and
therapeutic intervention should be done for patients with symptoms
suggestive of left ventricular dysfunction.
9.4.2
Sunitinib
Sunitinib malate is a receptor tyrosine kinase inhibitor of KIT and
PDGFR. Sunitinib also acts on vascular endothelial growth factor
receptors (VEGFR1-3), Fms-related tyrosine kinase (FLT3), colony-
stimulating factor (CSF)-1R, and the rearranged during transfection
(RET) protooncogene. Thus, sunitinib possesses potential
antiangiogenic activity in addition to antitumor action related to
receptor tyrosine kinase inhibition TKI. In the laboratory, sunitinib
inhibits some KIT mutant isoforms that are resistant to imatinib.
One of the largest trials on safety and efficacy of sunitinib in GIST
was published by Demetri and colleagues [102]. Patients with GIST
resistant to imatinib or patients intolerant of imatinib were included
in this trial. The primary end-point of this randomized, double-blind,
placebo-controlled study was time to tumor progression. Sunitinib
was given at 50 mg orally daily in 6-week cycles with 4 weeks on and
2 weeks off treatment. 312 patients were randomized in a 2:1 ratio
to receive sunitinib or placebo. The trial was terminated early after
