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SET2 Flashcards

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1
Q

What is the MOA of Ifosfamide?

A

Nitrogen mustard alkylating agent and given with Mesna (thiol donor) to prevent hemorrhagic cystitis just like cyclophosphamide

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2
Q

What are the main adverse effects of 6-MP

A

Myelosuppression and increased LFTs

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3
Q

True or False: Steroids can decrease the efficacy of Ipilimumab

A

False; so if someone gets an autoimmune issue can give steroids

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4
Q

Name 3 adverse effects of 5-FU

A

Severe myelosuppression, cardiotoxicity in the form of coronary vasospasm, and tear duct stenosis

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5
Q

What drug is known to cause a cold-sensitive neuropathy and even cold-sensitive laryngospasm? When does this occur?

A

Oxaliplatin; it can occur shortly after transfusion and is usually transient

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6
Q

What is the MOA of Ara-C (Arabinosylcytarabine)?

A

It is a PYRIMIDINE antimetabolite that inhibits DNA synthesis (S phase)

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7
Q

What anti-CD30 conjugate is approved for Hodgkin after relapse and in anaplastic large cell lymphoma after failure of at least 1 regimen?

A

Brentuximab vedotin

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8
Q

Deficiency in UGT1A1 in a patient being given Irinotecan can predispose to what problem?

A

Toxicity: prolonged myelosuppression

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9
Q

What should you be concerned for in pt being tx with R-CHOP who develops neuro Sx and MRI shows large non-enhancing lesion?

A

Progressive Multifocal Leukencephalopathy; Rituximab, Brentuximab, and Ofatumumab all cause reactivation of JC virus

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10
Q

How is methotrexate excreted?

A

Renally, and often need to alkalinize urine if giving high dose MTX

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11
Q

What drug is a prodrug of 5-FU that can be taken orally?

A

Capecitabine

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12
Q

Deficiency of what enzyme can lead to Irinotecan toxicity?

A

UGT1A1 which is an enzyme of the glucuronidation pathway; leads to prolonged myelosuppression

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13
Q

Why cant you use G-CSF to support neutropenia in Hodgkin pt receiving ABVD?

A

G-CSF increases Bleomycin Pulmonary toxicity

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14
Q

What is the dose limiting toxicity of bolus 5-FU?

A

Myelosuppression + Cardiotoxicity (vasospasm); additionally, when given in colon CA, there are better response rates to infusional dosing than bolus anyway

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15
Q

What HEENT complaint might a patient on 5-FU have?

A

They can get tear duct stenosis

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16
Q

Erlotinib, Gefitinib, and Afatinib are approved in what setting in lung cancer?

A

Stage IV lung cancer that harbor the exon 19 OR exon 21 EGFR mutations

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17
Q

Which interferon can be used in some melanoma patients?

A

Interferon-alpha-2b

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18
Q

What should you be concerned for in a patient with FOLFOX on warfarin?

A

The infusional 5-FU can decrease warfarin metabolism leading to supratherapeutic INR, switch to LMWH

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19
Q

Why is leucovorin able to “rescue” cells when given with HD MTX?

A

It gets converted to folic acid derivatives like tetrahydrofolate but does NOT need dihydrofolate reductase to do this; of note it, for some reason, does NOT rescue cancer cells

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20
Q

True or False: a rash in a patient on Erlotinib is a sign that you should stop the drug

A

False, it actually predicts a good response to therapy

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21
Q

If a patient with ovarian CA is receiving infusion of paclitaxel and carboplatin and has infusion rxn what is the likely culprit?

A

Paclitaxel; reaction to cremophor, slow the infusion

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22
Q

What are the main side effects of Ipilimumab?

A

Can exacerbate autoimmune phenomena

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23
Q

What are the drugs in MVAC what is a situation when this can be used?

A

A regimen used in muscle-invaseive bladder CA; MTX, VinBLASTINE, Doxorubicin, Cisplatin

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24
Q

What is radiation recall and what drugs can cause it?

A

Inflammatory reaction at site of prior radiation when certain chemo agents administered; Adriamycin, Paclitaxel, Docetaxel, Gemcitabine, Capecitabine

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25
Which causes reversible cardiotoxicity anthracyclines or trasztuzumab?
Trasztuzumab so if the EF starts to drop (i.e. \>16% of baseline) you should hold it and re-evaluate 4-8w
26
What is the terminal enzyme in the process of converting capecitabine to 5-FU
Thymidine phosphorylase
27
The CONFIRM study determined the optimal dose of Fulvestrant to be what?
500 mg was better than 250 mg
28
What drug, derived from the plant Cephalotaxus fortunei, inhibits the initial protein elongation step and is approved for chronic or acclerated phase CML resistant to two or more TKIs?
Omacetaxine mepesuccinate
29
When is Interferon-alfa-2b used in melanoma?
In patients with high risk of recurrence such as +SLNB or Breslow thickness \> 4mm
30
What kind of drug is Docetaxel and what is its major adverse effect? How is it excreted?
Taxane that causes severe neutropenia and anemia (myelosuppression) and is excreted hepatically; do not give if bilirubin \>7
31
What is XELOX?
Capecitabine + Oxaliplatin; no leucovorin
32
What are the adverse effects of Sunitinib (i.e. for RCC)?
HTN (an on-target effect), Hand-Foot syndrome, stomatitis, hypothyroidism, CHF, adrenal insufficiency
33
Name two cancer drugs that can cause HUS
Gemcitabine and Mitomycin C
34
True or false: Denosumab is noninferior to Zoledronic acid in delaying skeletal events in patients with advanced metastatic CA to bone or myeloma
True you can use either one, zoledronic acid more common though
35
Gemcitabine is a pyrimidine analog that is metabolized within cells to what active nucleoside forms? What is their intracellular effect?
Gemcitabine diphosphate: inhibits ribonucleotide synthesis; Gemcitabine triphosphate: competes to be incorporated into DNA and halts DNA synthesis
36
Fully explain the process by which Capecitabine is converted to 5-FU
Capecitabine converted to 5'-DFCR in liver by carboxylesterase; in the tissue the cytidine deaminase converts to 5'-DFUR and finally in the tumor cell THYIDINE PHOSPHORYLASE converts to 5-FU
37
How is the use of leucovorin in FOLFOX different from its use when given with HD MTX?
In HD MTX it is "Leucovorin Rescue"; in FOLFOX it increases the intracellular pool of 5, 10, methylenetetrahydrofolate which further increases inhibition of thymidylate synthase
38
True or False: Only cyclophosphamide causes hemorrhagic cystitis, ifosfamide does not
False, they both do and both should be given with Mesna
39
What are the two mutations that can confer EGFR TKIs?
EGFR gene T790M mutation which is the most common cause; also the MET-protooncogene can serve as resistance mechanism in 20%
40
Thymidilate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase are all inhibited by this drug
Pemetrexed
41
What is a standard emetic ppx in patients on High Risk Emetic Chemo (3)
Palonosetron 0.25 mg IV + Dexamethasone 12 mg IV + Fosaprepitant 150 mg IV
42
What mutation confers resistance to EGFR TKIs in 50% of patients who are resistant?
T790M in the EGFR gene
43
Why can Ifosfamide (nitrogen mustard alkylating agent) lead to severe encephalopathy?
It's breakdown product chloroacetylaldehyde can cause this issue
44
What are the adverse effects of Tamoxifen?
Endometrial CA, Cataracts, Strokes, Hot Flashes, DVTs
45
Which drug is truly an ER antagonist without ANY agonist activity
Fulvestrant
46
In addition to producing radical oxygen species, anthracyclines also inhibit what enzyme?
Topoisomerase II
47
What are some EGFR TKIs for lung CA (3)? What are two EGFR antibodies for colon CA?
Erlotinib, Gefitinib, and Afatinib; Cetuximab and Panitumumab
48
What is the MOA of Fulvestrant and when is it used?
It is a total ER antagonist without any partial agonist fxn, it downregulates the estrogen receptor and is used in post-menopausal women with ER + breast CA that have had progression after prior endocrine therapy
49
What kind of drug is Bosutinib?
A TKI used to tx CML; can cause diarrhea
50
What is the active metabolite of Irinotecan?
SN-38; it is 1000x more potent than irinotecan
51
How is Capecitabine excreted?
Renally; is GFR \<30 do not give, if GFR is 30-50 then dose reduce by 25%
52
What enzyme helps to detoxify Halogenated Pyrimidines (i.e. Fluoro-uracil), deficiencies of which can lead to toxicities?
Dihydropyridine Dehydrogenase
53
What supportive agent can increase the risk of Bleomycin pulmonary toxicity and so should not be given with ABVD?
G-CSF (i.e. Neupogen, Neulasta)
54
What are the two general ways to dose 5-FU in colon CA? Which is better and why?
Bolus or Infusional. The dose limiting toxicity of bolus 5-FU is myelosuppression and cardiotoxicity and also, there are better response rates to infusional so infusional is better.
55
Name 3 cancer monoclonal Abs that can lead to reactivation of JC virus
Rituximab, Ofatumumab, and Brentuximab
56
Why does paclitaxel often cause hypersensitivity reactions? What kind of reactions are there?
Due to the Cremophor vehicle. Can lead to sinus bradycardia so be careful if hx of ischemia or on AV nodal blocking drugs
57
What are the best antidepressants to give when given with Tamoxifen?
Citalopram and Venlafaxine, don't inhibit CYP2D6 which others do, leading to build up of endoxifen
58
What is Temozolamide often used for? What ppx do they need and why?
Glioblastoma multiforme; Bactrim because it causes significant lymphopenia and can therefore get Pneumocystis pneumonia
59
What does Brentuximab vedotin target?
CD30
60
Discuss early and late diarrhea from Irinotecan (i.e. I ran to the can)
Early Diarrhea within 24 h is cholinergic mediated and responds to atropine; Late diarrhea is at least 24 h out and tx with loperamide and FQs
61
How should you deal with dosage of 6-MP if allopurinol is being given?
Dose reduce by 50%
62
Why do patients get infusion reactions to paclitaxel and how to you manage?
Due to the Cremophor and the tx is to slow the rate of infusion
63
Deficiencies in what enzyme can lead to 5-FU toxicity
Dihydropyridine Dehydrogenase
64
Name two conditions that Brentuximab vedotin can be used in
Hodgkin after relapse from autoHSCT or failure of at least 2 chemo options; anaplastic large cell lymphoma that is CD30+ after failure of one tx
65
What study showed that LMWH is better than warfarin in cancer related anticoagulation?
CLOT study
66
What kind of cardiotoxicity occurs with 5-FU? What method of dosing ameliorates this?
Coronary Vasospasm, not as bad if given infusionally
67
During which part of the cell cycle does methotrexate act, MOA?
S phase cant make DNA or RNA; inhibits dihydrofolate reductase which is involved in tetrahydrofolate synthesis; by doing so thymidine can be made into purines
68
What study showed that Fulvestrant 500 mg monthly had better PFS than 250 mg monthly
CONFIRM study
69
What is the MOA of topotecan? How is it excreted?
It is a topoisomerase I inhibitor (can be used in metastatic ovarian CA, for example); renally
70
Which EGFR inhibitor can only be given in k-ras wild type metastatic colon CA?
Cetuximab
71
What three enzymes are inhibited by Pemetrexed
Thymidylate synthase, dihydrofolate reductase, and glycinamde ribonucleotide formyltransferase
72
What is the main adverse effect of Bosutinib?
Diarrhea
73
What kind of antibody is Ipilimumab?
Anti-CTLA4 (CTLA = Cytotoxic T Lymphocyte Associated protein)
74
How is Irinotecan excreted?
Hepatic excretion; the active metabolite, SN-38, is glucuronidated so in pt with UGT1A1 def (Gilbert's) it should not be given because it will cause prolonged myelosuppression
75
Name the pyrimidines
Cytosine, Uracil, Thymine
76
What are the oral and IV forms of neurokinin-1 antagonists?
PO = aprepitant; IV = fosaprepitant
77
True or false: cisplatin and carboplatin are equally efficacious for bladder CA
False, they usually are but here you have to use CISPLATIN i.e. in MVAC
78
What is SN-38?
This is the active metabolite of Irinotecan that actaully inhibits Topisomerase I and prevents DNA unwinding
79
What is Omacetaxine mepesuccinate?
It is a drug approved for chronic or accelerated phase CML with resistance to two or more TKIs
80
What tyrosine kinases does Imatinib inhibit in CML and GIST?
CML = BCR-ABL; GIST = c-kit (CD117)
81
What is the MOA of Irinotecan?
It is a topoisomerase I inhibitor and so prevents DNA from unwinding; active metabolite is SN-38
82
Why is it that Rituximab can lead to severe myelosuppression?
There is high CD20 expression in the BM
83
What is CD117
Mast/Stem cell growth factor receptor (SCFR) which is also known as protooncogene c-kit; so expressed in mastocytosis and GIST where c-kit mutation is driver and Tx with imatinib
84
What infusion, initally thought to decrease oxaliplatin related neuropathy in FOLFOX, has since been debunked?
Infusion of calcium and magnesium, has NOT been shown to reduce either cumulative neurotoxicity or acute neuropathy
85
Which drug is an IgG2 fully humanized antibody to EGFR?
Panitumumab
86
What drug is known to be increased by allopurinol? What is a regimen this is used in?
6-MP (6-mercaptopurine); POMP (6-MP, MTX, Vincristine, Prednisone) which is maintenance for Philadelphia negative ALL
87
What are the adverse effects of capecitabine?
Hand-Foot syndrome, diarrhea, stomatitis, and neutropenia
88
A patient with a melanoma that has been excised but has high risk of recurrence such as +SLNB or Breslow thickness \> 4 mm can be tx with what agent?
IFN-alfa-2b; can cause fevers and psych issues

MALIGNANT HEME (12 decks)

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