mainstay therapy for CML?
tyrosine kinase inhibitors
Imatinib
- MOA?
- PEARLS?
- major side effects?
- blocks Bcr-Abl’s ability to phosphorylate and activate proteins
- first line therapy for CML
- hepatotoxicity, GI bleeding, tumor lysis syndrome
Nilotinib
- MOA?
- uses?
- major side effects?
- similar to Imatinib
- used in Bcr-Abl mutants resistant against Imatinib but ineffective against T315I (CML)
- myelosuppression
Dastinib
- MOA?
- uses?
- major side effects?
- similar to Imatinib
- used in Bcr-Abl mutants resistant to Imatinib but ineffective against T315I (CML)
- myelosuppression, pulmonary arterial hypertension
Bosutinib
- MOA?
- uses?
- major side effects?
second line for CML
- ATP competitive inhibitor of Bcr-Abl
- at strains resistant or tolerant to first line therapy
- GI toxicity, hepatic toxicity, renal toxicity
Ponatinib
- MOA?
- PEARLS?
- major side effects?
second line therapy for CML
effective against T315I mutant!
boxed warning!
four types of melanoma?
- cutaneous
- acral
- mucosal
- uveal
BRAF mutations encode ______
most common mutation?
second most common?
serine threonine kinase
- BRAFV600E
- BRAFV600K
Vemurafenib
- MOA?
- uses?
- major side effects?
- contraindications?
- inhibits BRAF kinase
- unresectabe stage III or IV metastatic melanoma w/ BRAFV600 mutations
- new primary cutaneous melanoma, QT prolongation
- cannot be used in melanomas with wild-type BRAF mutation
Dabrafenib
- uses?
- major side effects?
- contraindications?
- unresectabe stage III or IV metastatic melanoma w/ BRAFV600 mutations
- serious febrile fever rxns; hypotension, rigors/chills, dehydration, kidney failure
- cannot be used in melanomas with wild-type BRAF mutation
Trametinib
- MOA?
- major side effects?
- contraindications?
- inhibits MEK which is an extracellular signal/regulated kinase
- serious skin toxicity, retinal vein occlusion
- cannot be used in melanomas with wild-type BRAF mutation
which epidermal growth factor receptor (EGFR) is overexpresed in breast, ovarian, and gastric cancers?
ErbB2/her2/neu
types of non-small cell lung cancers?
squamous cell, adenocarcinoma, large-cell
first-line treatment options are use for tumors for which exon mutations in the EGFR?
MOA?
- exon 19 deletion
- exon 21 (L858R) mutation
MOA = inhibit kinase function of EGFR and inhibition of downstream signaling
Erlotinib
- class?
- side effects?
- drug interactions?
- EGFR-inhibitor
- N/V, interstitial lung disease
- drugs that target CYP3A4, proton pump inhibitors, warfarin
Gefitinib
- class?
- side effects?
- EGFR-inhibitor
2. interstitial lung disease, liver damage, GI perforation
Afatinib
- class?
- side effects?
- EGFR-inhibitor
2. N/V, rash, fatigue, pulmonary toxicity
- drug target in Anaplastic large cell lymphoma?
2. what fusion product becomes constitutively active?
- ALK - cell surface receptor tyrosine kinase
2. fusion between EML4+ALK genes at Ch2 become constitutively active
Crizotinib
- class?
- uses?
- side effects?
- ATP-competitive inhibitor of ALK
- ALK (+) metastatic NSCLC (oral use)
- visual disorders, N/V, pulmonary embolism
Ceritinib
- class?
- uses?
- side effects?
- ALK inhibitor
- oral Tx for ALK(+) metastatic NSCLC progressed on Crizotinib or intolerant patients
- N/V, elevated liver enzymes, QT prolongation
Trastuzumab
- class?
- MOA?
- uses?
- side effects?
- Anti-ErbB2 humanized monoclonal
- prevents transduction of proliferation & survival signals, eventual degradation of the receptor
- node (+) or (-) breast cancer that includes ErbB2 (part of combo) and metastatic breast cancer (part of combo)
- Boxed warning - cardiomyopathy, infusion rxns, pulmonary toxicity
Pertuzumab
- class?
- MOA?
- uses?
- side effects?
- Anti-ErbB2 humanized monoclonal
- prevents ErbB2 interaction which inhibits proliferation signals
- in combo therapy for ErbB2 (+) breast cancer with no history of anti-ErbB2 therapy
or in neoadjuvant setting with Trastuzumab + docetaxel for treatment of early breast cancer
- LV dysfunction, CHF, embryo-fetal toxicity, allergic reaction
Nivolumab
- class?
- uses?
- side effects?
- humanized monoclonal antibody that inhibits PD1
- unrectable or mestastatic melanoma in combo w/ ipilimumab for BRAF wild-type tumors
advanced/metastatic squamous NSCLC that has progressed on platinum-based therpay
- rash, N/V, constipation, severe immune mediated side effects
Pembrolizumab
- class?
- uses?
- side effects?
- humanized monoclonal antibody that inhibits PD1
- 1st line therapy for advanced NSCLC that has increased expression of PD-L1 but no EGFR or ALK mutatnts, no history of previous chemo
malignancies with microsatellite instability or mismatch repair deficiencies
colorectal cancers that have progressed on previous therapies
second line for advanced NSCLC that have progressed on platinum-based therapy
advanced urothelial bladder cancers
- pneumonitis, colitis, endocrinopathies, nephritis, renal failure, hepatitis, complications of stem cell transplant
