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What are the major class SEs of alkylating agents?
- secondary leukemias
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?
- 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?
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?
Which alkylating agent is indicated for glioblastoma?
What is the dose-limiting toxicity of carboplatin?
- (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?
- because it is so highly emetogenic
Which alkylating agent is dosed using the Calvert equation? What is the significance of this?
- it means carboplatin is dosed based on estimated GFR rather than BSA
What are the major class SEs of antimetabolites?
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?
- purine analogues are antimetabolites
Name 4 pyrimidine analogues. What class do these fall under?
- 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?
- to prevent dose limiting toxicities (myelosuppression and mucositis)
With which antimetabolite is premedication with vitamin B12 and folic acid required? Why?
- to reduce the severity of myelosuppression
Which antimetabolite requires antimicrobial prophylaxis? Why?
- d/t high risk of opportunistic infections
Which antimetabolite is an oral prodrug that is converted to 5-FU?
Which antimetabolite may need prophylactic dexamethasone eye drops prior to and following HiDAC? Why?
- d/t conjunctivitis/keratitis
What are the major class SEs of antimicrotubules?
- peripheral neuropathy
- note - low n/v potential
What are the 4 subcategories of antimicrotubules?
- vinca alkaloids
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?
- 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?
- 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?
- approved Nov 2010 for metastatic breast cancer previously treated with an anthracycline and a taxane
Which antimicrotubules cannot be given intrathecally?
Which antimicrotubule requires prophylaxis with dexamethasone? Why?
- d/t hypersensitivity reactions
What are the major class SEs of enzyme inhibitors?
- 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?
- Topo I inhibitors are enzyme inhibitors
Name 5 topoisomerase II inhibitors. What class are these?
- topo II inhibitors are enzyme inhibitors
What med is an epipodophyllotoxin? What class is this?
- epipodophyllotoxins are enzyme inhibitors
What are risk factors for cardiac toxicity with anthracyclines?
- 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?
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?
Name 7 monoclonal antibodies
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?
- ofatumumab (APAP, antihistamine, & IV corticosteroid)
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?
Which monoclonal antibody is approved for CLL refractory to fludarabine and alemtuzumab?
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?
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?
Which targeted therapy is a multi-tyrosine kinase inhibitor of VEGF (1,2, & 3), PDGF, and Kit receptors as well as other intracellular kinases?
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?
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?
Which tyrosine kinase inhibitor is indicated for breast cancer?
With which targeted therapy must we monitor EKG, CBC with differential, and bowel function?
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?
Which drug is approved to treat cutaneous T-cell lymphoma in patients who have received at least 1 prior therapy?