Cancer Chemotherapeutics

Question 1

What are two vinca-alkaloids?

Answer 1

Vincristine and vinblastine (-stine)

Question 2

What is the mechanism for vinca-alkaloids?

Answer 2

They inhibit microtubule polymerization

Question 3

What are two taxans?

Answer 3

Paclitaxel and docetaxel

Question 4

What is the mechanism for taxans?

Answer 4

They inhibit microtubule depolymerization

Question 5

What is similar between vinca-alkaloids and taxans?

Answer 5

They inhibit mitotic spindle function and are non-targeted chemotherapies

Question 6

What are adverse effects of microtubule inhibitors?

Answer 6

They have general adverse effects seen in non-targeted therapies but some have specific AEs
- GI cells: Diarrhea, mucositis, nausea/vomiting
- BM cells: leukopenia, thrombocytopenia, anemia (all together= pancytopenia)
- Hair follicles: alopecia

Question 7

What is a unique adverse effect found in paclitaxel?

Answer 7

Anaphylaxis
–> best to give corticosteroid and anti-histamine before using this to eliminate chance of allergic rxn

Question 8

What are two unique adverse effects found in docetaxel?

Answer 8

Anaphylaxis and fluid retention
–> best to give corticosteroid and anti-histamine before

Question 9

What are two unique adverse effects found in vincristine?

Answer 9

Extravasation (monitor for pain, swelling, poor blood return) and constipation (autonomic neuropathy so give laxative and stool softener)

Question 10

What is a two unique adverse effects found in vinblastine?

Answer 10

Extravasation (monitor for pain, swelling, poor blood return) and myelotoxic

Question 11

What chemotherapeutics cause peripheral neuropathy?

Answer 11

Paclitaxel and vincrestine

Question 12

6- Mercaptopurine

Answer 12

MOA: Inhibits de novo purine synthesis
AE: Hepatotoxicity
DDI: Allopurinpol and febuxostat (uric acid reducer)

Question 13

Methotrexate

Answer 13

MOA: inhibits de novo purine synthesis; also inhibits DHF-reductase (so inhibitor of thymidylate synthase and de novo purine synthase)
AEs: hepatotoxicity (BBW), bone marrow suppression (BBW); used with leucovorin to help limit toxic side effects
CIs: pregnancy (BBW)

Question 14

5-fluoruracil

Answer 14

MOA: inhibits thymidylate synthase
AEs: hand-foot syndrome (skin toxicity)

Question 15

Capecitabine

Answer 15

MOA: Oral prodrug of 5-fu

Question 16

Hydroxyurea

Answer 16

MOA: inhibits ribonucleotide reductase

Question 17

DNA intercalators: doxorubicin, doumorubicin, dactinomycin

Answer 17

MOA: intercalate into DNA and disrupt the progress of the replication fork (distorts the helix)
AEs: cardiomyopathy (prevention of this by using dexrazoxane which is an iron chelator), urine discoloration (red), and vesicant (can cause skin necrosis)

Question 18

Cytarabine aka Ara-C

Answer 18

MOA: incorporates into DNA, blocks elongation
AEs: hepatotoxicity (BBW), BM suppression (BBW), cerebellar toxicity

Question 19

TOPO inhibitors/DNA clearing agents: irinotecan, topotecan, etoposide

Answer 19

MOA: inhibit topoisomerase (freezes enzyme after cleavage before ligation) which causes DNA strand breaks
AEs: severe diarrhea (irinotecan is AChE inhibitor and can cause cholinergic symptoms–> use atropine before giving)

Question 20

Bleomycin

Answer 20

MOA: produces ss/ds DNA breaks by a complex mechanism involving bleomycin, oxygen and ferrous iron
AEs: pulmonary fibrosis (major limitation) and hypersensitivity (anaphylactic reactions)

Question 21

Cyclophosphamide

Answer 21

MOA: alkalates DNA and causes inter-strand crosslinks –> strand breaks and p55 helps cause apoptosis
AEs: hemorhagic cystitis (bleeding/bladder inflammation from formation of acrolein; prevent by excessive hydration and MESNA), secondary malignancies, gonadotoxic

Question 22

Cisplatin

Answer 22

MOA: forms platinum adduct to cross link guanines and causes apoptosis
AEs: nephrotoxicity (b/c cleared by kidney) and can cause hypomagnesmia (monitor Mg, K, SCr; prevent via hydration and amifostin), ototoxicity

Question 23

Oxaliplatin

Answer 23

MOA: platinum agent
AEs: less nephrotoxicity and less ototoxicity but neurotoxic –> can cause pharyngolaryngeal dysesthesia which can be caused/worsened by cold temp

Question 24

EGFR-TKIs: erlotinib, gefitinib, brigatinib

Answer 24

MOA: blocks EGFR-Tyrosine kinase
AEs: rash (up to 75%), diarrhea, steven-johnson syndrome

Question 25

HER-2/EGFR-TKI: Lapatinbib

Answer 25

MOA: blocks HER-2 (and EGFR) tyrosine kinase
AEs: cardiotoxic (decreases LVEF) and hepatotoxic

Question 26

BCR-aBL TKI: imatinib, dasatinib, nilotinib

Answer 26

MOA: blocks BCR-Abl tyrosine kinase
AEs: GI, hepatotoxicity, QT prolongation (nilotinib specifically as there is a BBW)

Question 26

BCR-aBL TKI: imatinib, dasatinib, nilotinib

Answer 26

MOA: blocks BCR-Abl tyrosine kinase
AEs: GI, hepatotoxicity, QT prolongation (nilotinib specifically as there is a BBW)

Question 27

VEGFR TKI: Sunitinib

Answer 27

MOA: blocks VEGFR TK
AE: hepatotoxicity (BBW), hypertension, thromboembolism

Question 28

Cetuximab

Answer 28

MOA: monoclonal antibody to EGFR
AEs: rash, GI issues, hypomagnesemia (EGFR targets TRMP6 so more Mg is reabsorbed)

Question 29

Trastuzumab

Answer 29

MOA: monoclonal antibody against HER-2
AEs: cardiotoxic

Question 30

Bevacizumab

Answer 30

MOA: monoclonal antibody to VEGFR
AEs: hypertension, thromboembolism, poor wound healing