-
What are the major class SEs of alkylating agents?
- myelosuppression
- N/V
- secondary leukemias
- sterility
- infertility
-
Name the 3 categories of alkylating agents and their MOAs
- 1. Nitrogen mustards - produce alkylation of DNA through the formation of reactive intermediates that attack nucleophilic sites
- 2. Triazenes - induce methylation of nucleic acids leading to direct DNA damage
- 3. Platinum agents - covalently bind to DNA disrupting DNA function
-
Name 3 nitrogen mustards. What class are these?
- 1. bendamustine
- 2. cyclophosphamide
- 3. ifosfamide
- Nitrogen Mustards are Alkylating Agents
-
Name a triazene. What class are triazenes?
- temozolomide
- Triazenes are Alkylating Agents
-
Name 3 platinum agents. What class are these?
- 1. carboplatin
- 2. cisplatin
- 3. oxaliplatin
- Platinum agents are Alkylating agents
-
What agent causes reversible peripheral sensory neuropathy that is precipitated by exposure to cold temps, cold objects, or cold beverages?
oxaliplatin
-
Which alkylating agents cause hemorrhagic cystitis?
- cyclophosphamide and ifosfamide
- usually assoc with high doses (with cyclo)
- may need MESNA for prevention with cyclophosphamide (a chemoprotectant). It is required with ifosfamide.
-
The immunosuppression associated with which alkylating agent is associated with AML?
cyclophosphamide
-
Which alkylating agent is indicated for glioblastoma?
temozolomide
-
What is the dose-limiting toxicity of carboplatin?
- thrombocytopenia
- (counsel regarding bleeding risk)
-
Which alkylating agent is given with ondansetron on day 1, aprepitant on days 1-3, and dexamethasone on days 1-4? Why?
- cisplatin
- because it is so highly emetogenic
-
Which alkylating agent is dosed using the Calvert equation? What is the significance of this?
- Carboplatin
- it means carboplatin is dosed based on estimated GFR rather than BSA
-
What are the major class SEs of antimetabolites?
- myelosuppression
- n/v
- mucositis
-
What are the 3 categories of antimetabolites?
- Folate antagonists
- Purine analogues
- Pyrimidine analogues
-
Name 3 folate antagonists and what class they fall under
- 1. methotrexate
- 2. pemetrexed
- 3. pralatrexate
- folate antagonists are antimetabolites
-
Name a purine analog. What class is this?
- fludarabine
- purine analogues are antimetabolites
-
Name 4 pyrimidine analogues. What class do these fall under?
- capecitabine
- cytarabine
- fluorouracil
- gemcitabine
- pyrimidine analogues are antimetabolites
-
By what route is methotrexate metabolized?
hepatically and renally
-
What antimetabolite requires use of leukovorin when high dose therapy is administered? Why?
- methotrexate
- to prevent dose limiting toxicities (myelosuppression and mucositis)
-
With which antimetabolite is premedication with vitamin B12 and folic acid required? Why?
- pemetrexed
- to reduce the severity of myelosuppression
-
Which antimetabolite requires antimicrobial prophylaxis? Why?
- fludarabine
- d/t high risk of opportunistic infections
-
Which antimetabolite is an oral prodrug that is converted to 5-FU?
capecitabine
-
Which antimetabolite may need prophylactic dexamethasone eye drops prior to and following HiDAC? Why?
- cytarabine
- d/t conjunctivitis/keratitis
-
What are the major class SEs of antimicrotubules?
- myelosuppression
- peripheral neuropathy
- note - low n/v potential
-
What are the 4 subcategories of antimicrotubules?
- vinca alkaloids
- taxanes
- epothilones
- misc.
-
Which 2 meds are vinca alkaloids. Which class are these? What is their MOA?
- vincristine and vinorelbine
- vinca alkaloids are antimicrotubules
- MOA - binds to tubulin leading to microtubule disassembly leading to inhib of cell mitosis
-
Which 3 meds are taxanes? What class do these fall under? What is their MOA?
- cabazitaxol
- docetaxel
- paclitaxel
- Taxanes are antimicrotubules
- MOA - bind to microtubules, stabilize assembly, inhibiting cell mitosis
-
Which med is an epothilone? What class is this? What is its MOA?
- ixabepilone
- epothilones are antimicrotubules
- MOA - binds to microtubules and stabilizes assembly inhibiting cell mitosis
-
Which medication falls under the misc. category of antimicrotubules? What is it approved for?
- eribulin
- approved Nov 2010 for metastatic breast cancer previously treated with an anthracycline and a taxane
-
Which antimicrotubules cannot be given intrathecally?
vinca alkaloids
-
Which antimicrotubule requires prophylaxis with dexamethasone? Why?
- docetaxel
- d/t hypersensitivity reactions
-
What are the major class SEs of enzyme inhibitors?
- myelosuppression
- n/v
- cardiac toxicity (anthracyclines only)
-
What are the 3 categories of enzyme inhibitors and their MOAs?
- Topoisomerase I Inhibitors - inhibit DNA winding enzyme, topo I, ultimately producing DNA damage
- Topoisomerase II Inhibitors (anthracyclines) - cause DNA intercalation interfering with uncoiling and inhibition of topo II thereby interfering with DNA repair. Also cause formation of free radicals, chemically damaging cell structures.
- Epipodophyllotoxins - similar to topo II inhibitors
-
What drug is a topoisomerase I inhibitor? What class is this?
- irinotecan
- Topo I inhibitors are enzyme inhibitors
-
Name 5 topoisomerase II inhibitors. What class are these?
- daunorubicin
- doxorubicin
- epirubicin
- idarubicin
- mitoxantrone
- topo II inhibitors are enzyme inhibitors
-
What med is an epipodophyllotoxin? What class is this?
- etoposide
- epipodophyllotoxins are enzyme inhibitors
-
What are risk factors for cardiac toxicity with anthracyclines?
- children
- IV bolus vs. infusion
- cumulative doses > 350 mg/m2age > 70
- prior radiation to mediastinum
- underlying heart disease
- previous anthracycline-based therapy
- concurrent use of other cardiotoxic drugs
-
What is the major dose limiting toxicity of irinotecan?
diarrhea
-
Which enzyme inhibitors discolor urine a red/orange color? Blue/green?
- red/orange: daunorubicin, doxorubicin, idarubicin
- blue/green: mitoxantrone
-
What is the suggested lifetime dose of doxorubicin? Daunorubicin?
- Doxorubicin: 450-500 mg/m2
- Daunorubicin: 900-1000 mg/m2
-
Which topo II inhibitor has less risk of cardiac toxicity than the others?
mitoxantrone
-
Name 7 monoclonal antibodies
- alemtuzumab
- bevacizumab
- cetuximab
- ofatumumab
- panitumumab
- rituximab
- trastuzumab
-
What is the target of alemtuzumab?
CD52+ antigen present on T and B cell leukemia/lymphoma cells
-
Which monoclonal antibodies require prophylaxis with diphenhydramine +/- APAP for infusion related reaction?
- alemtuzumab
- cetuximab
- ofatumumab (APAP, antihistamine, & IV corticosteroid)
- rituximab
- trastuzumab
-
What is the target of bevacizumab?
VEGF receptors to inhibit angiogenesis
-
What is the target of cetuximab?
EGFR, mainly EGFR1, which is overexpressed in a variety of solid tumors
-
What is the target of ofatumumab?
CD20+ antigen present on B-lymphocytes and B-cell CLL
-
Which monoclonal antibody requires anti-infective prophylaxis d/t the high risk of infections?
alemtuzumab
-
Which monoclonal antibody is approved for CLL refractory to fludarabine and alemtuzumab?
ofatumumab
-
What is the target of panitumumab?
EGFR, mainly EGFR1 (expressed in variety of solid tumors)
-
What is the target of rituximab?
CD20+ antigen present on all B cells including lymphoma cells
-
What is the target of trastuzumab?
EGFR, specifically EGFR2 (aka HER2/neu) protein which is overexpressed on some breast cancer cells
-
Which drugs target the BCR-ABL oncogene in Philadelphia chromosome positive CML cell lines?
- dasatinib
- imatinib
- nilotinib
-
Which targeted therapy is used in pts resistant to imatinib?
dasatinib or nilotinib
-
Which drugs are tyrosine kinase inhibitors?
-
Which targeted therapy is an inhibitor of mTOR?
everolimus
-
Which targeted therapy is a multi-tyrosine kinase inhibitor of VEGF (1,2, & 3), PDGF, and Kit receptors as well as other intracellular kinases?
pazopanib
-
Which targeted therapies inhibit tyrosine and raf kinases and inhibit angiogenesis by internally blocking activation of VEGF and PDGF receptors?
sorafenib and sunitinib
-
Which targeted therapies are used for leukemias?
- dasatinib
- imatinib
- nilotinib
-
Which targeted therapies are used for solid tumors?
-
Which targeted therapies are used for renal cell carcinoma?
sorafenib, sunitinib, pazopanib, everolimus
-
Which tyrosine kinase inhibitor is indicated for stage IV NSCLC?
erlotinib
-
Which tyrosine kinase inhibitor is indicated for breast cancer?
lapatinib
-
With which targeted therapy must we monitor EKG, CBC with differential, and bowel function?
nilotinib
-
What is the MOA of all-trans retinoic acid?
binds to the retinoic acid receptor alpha gene on chromosome 17 which leads to cell proliferation and differentiation
-
What is the MOA of arsenic trioxide?
Induction of apoptosis, partial differentiation of fusion protein, inhibition of angiogenesis
-
What is the MOA of bleomycin?
causes direct DNA damage leading to single and double strand breaks
-
What is the MOA of romidepsin?
histone deacetylase inhibitor - inducing cell cycle arrest and apoptosis
-
What do we monitor for with all-trans retinoic acid?
retinoic acid syndrome - fever, respiratory distress, interstitial pulmonary infiltrates, weight gain
-
What is a significant SE of arsenic trioxide?
- QT segment prolongation - major cardiac arrhythmias
- also retinoic acid syndrome, peripheral neuropathy, fatigue, weight gain
-
What is the dose limiting toxicity of bleomycin?
pulmonary tox - sub acute or chronic interstitial pneumonitis
-
What is the suggested lifetime dose of bleomycin?
450 mg
-
Which drug is approved to treat cutaneous T-cell lymphoma in patients who have received at least 1 prior therapy?
romidepsin
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