Chronic myeloid leukemia drugs

Imatinib mesylate (Gleevec, Novartis Glivec in countries other than the United States) is a drug for the treatment of chronic myeloid leukemia (CML). CML is a result of a chromosomal problem and gives rise to high levels of white blood cells. An enzyme called BCR-ABL is involved. The BCR-ABL gene encodes a protein with elevated tyrosine kinase activity (see Exhibit 7.3). 

In some circumstances, the FDA processes drug reviews under the accelerated scheme. This mechanism is to review and approve drugs speedily for cases where effective therapies are lacking or in situations of rare diseases. One of the fastest approval times to date is the case of imatinib mesylate (Gleevec, Novartis—Exhibit 7.3) for the treatment of chronic myeloid leukemia (CML) it was approved in less than 3 months after the filing of an NDA with the FDA. Another example is the new AIDS drug indinavir (Crixivan, Merck), which was approved in a mere 42 days. 

Wang L et al (2008) Expression of the uptake drug transporter hOCTl is an important clinical determinant of the response to imatinib in chronic myeloid leukemia Clin Pharmacol Ther 83 258-264... 

This dynamic multidrug-targeted prevention technique has been proposed in the treatment of chronic myeloid leukemia and the positive results obtained with the newly introduced drugs nilotinib and dasatinib suggested that a combination of two or three kinase inhibitors, when carefully selected to cover all known resistant mutations, could shut off all mechanisms of escape. 

The possibility that melphalan and busulfan may cause additive lung damage has been discussed in the light of a 59-year-old patient with chronic myeloid leukemia who developed severe interstitial lung fibrosis after short-term sequential treatment with the two drugs (7). 

The crating drug concept is evaluated by revisiting a recent redesign of imatinib [15], the anticancer drug adopted to treat chronic myeloid leukemia (CML) [3, 4], As previously described in Chaps. 7 and 8, this inhibitor was originally designed to... 

Imatinib mesylate, a drug recently approved for the treatment of chronic myeloid leukemia (CML), can also be affected by St. John s wort. Because imatinib is primarily metabolized by CYP3A4 and is also a Pgp substrate, the usage of St. John s wort in combination with imatinib has resulted in a significant reduction in exposure to the drug compared to imatinib alone. This is potentially significant because therapeutic outcomes for patients with CML have been shown to correlate with the dose and drug concentrations of imatinib (87). 

Genetics has already been incorporated into the care of children with cancer an example is the Philadelphia Chromosome, a chromosomal anomaly produced as a result of reciprocal translocation between chromosomes 9 and 22 [t(9 22)(q34 qll)] that is most commonly seen as a marker of chronic myeloid leukemia [50]. The presence of this chromosomal anomaly is associated with altered prognosis—and the need for different therapy—when seen in the context of acute lymphoblastic leukemia in childhood [51], An area of oncology care where genetics has not been widely used has been in the evaluation—and possibly prevention—of adverse drug reactions [52],... 

However, the claimed selectivity often remains quite low. For instance, imatinib, originally developed as a highly selective inhibitor of the tyrosine kinase activity of c-ABL (approved for chronic myeloid leukemia), has subsequently been discovered to also inhibit tyrosine kinase activity of c-KIT and PDGFR. In that case, the lack of selectivity offers the opportunity to extend the clinical utility of the drug. ... 

A number of inhibitors of various tyrosine kinase enzymes are important new cancer drugs sunitinib (Sutent) is used for the treatment of certain kidney and GI cancers imatinib (Glivec) for chronic myeloid leukemia and GI tumours, and lapatinib (Tykerb/Tykerv) for breast and lung cancers. Bortezomib (Velcade), a proteasome inhibitor is used to treat multiple myeloma and is notable for being a boronic acid. 

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