Cancer Pharm: Anti-tumor antibiotics Flashcards
What are the major MOA of the anthracyclines?
- Inhibition of topoisomerase II
- Generation of free radicals
- DNA intercalation –> blocking of DNA and RNA synthesis
What is the dose limited toxicity associated with the anthracyclines?
- Myelosuppression mainly neutropenia
- Some cases, mucositis
What is a major AE associated with anthracyclines?
Cardiotoxicity; both an acute and chronic form
Which class of cancer drugs is associated with radiation recall rxns causing erythema and desquamation of the skin at sites of prior radiation?
Anthracyclines
Which anthracycline is more active in producing complete remissions and in improving survical in pt’s with acute myelogenous leukemia?
Idarubicin
What is the MOA of the anthracycline, Mitoxantrone?
- Binds and breaks strands of DNA
- Inhibits both DNA and RNA synthesis
Which AE is unique to the anthracycline, Mitoxantrone?
Blue discoloration of the fingernails, sclera, urine
What is Dexrazoxane and why is it used with anthracyclines?
- Iron-chelating agent
- To prevent or reduce anthracycline-induced cardiotoxicity in women w/ metastatic breast cancer that have received a cumulative dose (>300 mg/m2) of doxorubicin
What is the MOA of mitomycin?
Activated to an alkylating agent that cross-links DNA
What is the best available drug for use in combo w/ radiation therapy to attack hypoxic tumor cells?
Mitomycin
During which phase of the cell cycle is Mitomycin most active?
Active in ALL phases of cell cycle
What are 2 of the unique delayed toxicities associated w/ Mitomycin?
Mucositis and hemolytic-uremic syndrome
What are the 2 uses of Mitomycin?
- SCC of the anus in combo w/ 5-FU + radiation
- Intravesical tx of superficial bladder cancer
What is the MOA of bleomycin; arrests cells in which phase?
- DNA fragmentation and single/double strand breaks due to free radical formation
- Cells accumulate in G2 phase *Think ‘B’leomycin = bi- = 2*
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What is the dose limiting toxicity associated with bleomycin?
Pulmonary toxicity –> pneumonitis w/ cough, dyspnea, dry crackles on PE and infiltrates on CXR
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Tyrosine kinase inhibitors are metabolized by what CYP?
CYP3A4
The tyrosine kinase inhibitor, Imatinib, specifically inhibits what?
- BCR-ABL fusion protein
- Inhibits RTK’s for PDGFR and c-kit
What are some of the delayed toxicities associated w/ the tyrosine kinase inhibitor, Imatinib?
- Fluid retention w/ ankle and periorbital edema
- Myalgias
- CHF
- Diarrhea
What is the clinical use for the tyrosine kinase inhibitor, Imatinib?
- 1st line for chronic phase CML, in blast crisis, and as 2nd line for chronic phase CML that has progressed on prior IFN-α tx
- GI stromal tumors expressing c-kit
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What is the MOA for the tyrosine kinase inhibitors, Dasatinib and Nilotinib; how do they differ from Imatinib?
- Inhibitor of BCR-ABL, c-kit, and PDGFR-β tyrosine kinases
- Dasatinib binds active and inactive conformations of ABL kinase; while Nilotinib has higher binding affinity for ABL kinase
- Overcomes imatinib resistance from mutations in BCR-ABL kinase
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