Dabrafenib

tafinlar 2d
Brand name: Tafinlar®
IUPAC: N-[3-[5-(2-aminopyrimidin-4-yl)-2-tert-butyl-1,3-thiazol-4-yl]-2-fluorophenyl]-2,6-difluorobenzenesulfonamide
FDA approval: Yes
Usage:

Tafinlar is a targeted therapy that targets the mutated BRAF proteins (kinase) within the cancer cell. The BRAF gene plays an important role in both normal and cancer cells. This gene leads to the production of BRAF protein. This protein is normally part of a chain of molecules that relay a signal that tells cells how to grow and divide. A change in the BRAF gene (called a mutation) can alter the way that the BRAF protein works. Instead of waiting for its turn to signal a cell to divide or grow, the BRAF protein is out of control and signals all of the time, this out of control BRAF signaling may drive the uncontrolled growth of cancer cells. Tafinlar targets these changed BRAF proteins and may slow down the growth of cancer. 

How Tafinlar is given: 

  • Tafinlar is a pill, taken by mouth, twice daily. Take at least 1 hour before or 2 hours after a meal. 

  • Take Tafinlar exactly as prescribed. 

  • Swallow Tafinlar capsules whole. Do not crush, open or dissolve capsules. 

  • Do not change your dose or stop Tafinlar unless your health care provider tells you to. 

  • If you miss a dose, take it as soon as you remember. If it is too close to your next dose (within 6 hours), just take your next dose at your regular time. 

  • Do not take more than 1 dose of Tafinlar at one time. Call your health care provider right away if you take too much. 

  • The amount of Tafinlar that you will receive depends on many factors, your general health or other health problems, and the type of cancer or condition being treated. Current recommendation is for one tablet twice daily, higher doses do not always give a better response and may cause increased toxicity. Your doctor will determine your dose and schedule. 

Mechanism:

Dabrafenib is an inhibitor of some mutated forms of BRAF kinases with in vitro IC50 values of 0.65, 0.5, and 1.84 nM for BRAF V600E, BRAF V600K, and BRAF V600D enzymes, respectively. Dabrafenib also inhibits wild-type BRAF and CRAF kinases with IC50 values of 3.2 and 5.0 nM, respectively, and other kinases such as SIK1, NEK11, and LIMK1 at higher concentrations. Some mutations in the BRAF gene, including those that result in BRAF V600E, can result in constitutively activated BRAF kinases that may stimulate tumor cell growth. Dabrafenib inhibits BRAF V600 mutation-positive melanoma cell growth in vitro and in vivo. Dabrafenib and trametinib target two different tyrosine kinases in the RAS/RAF/MEK/ERK pathway. Use of dabrafenib and trametinib in combination resulted in greater growth inhibition of BRAF V600 mutation-positive melanoma cell lines in vitro and prolonged inhibition of tumor growth in BRAF V600 mutation positive melanoma xenografts compared with either drug alone. 

Side effects:

Important things to remember about the side effects of Tafinlar: 

  • Most people do not experience all of the side effects listed. 

  • Side effects are often predictable in terms of their onset and duration. 

  • Side effects are almost always reversible and will go away after treatment is complete. 

  • There are many options to help minimize or prevent side effects. 

  • There is no relationship between the presence or severity of side effects and the effectiveness of the medication. 

The following side effects are common (occurring in greater than 30%) for patients taking Tafinlar: hyperglycemia, hyperkeratosis, hypophosphatemia, and headache. 

These side effects are less common side effects (occurring in about 10-29%) of patients receiving Tafinlar: fever, joint pain, papilloma (warts/growths), hair loss, hand-foot syndrome (palmar-plantar erythrodyesthesia), increased alkaline phosphatase, rash, back pain, cough, muscle aches, constipation, and nasopharyngitis.