Cancer Chemotherapy Drugs

Question 0

Trastuzumab (herceptin)

Answer 0

First antibody against oncogene
Anti-HER2 growth factor, Ag binding region fused to IgG
Used with chemotherapy: doxorubicin and cyclophosphamide
Better with pertuzumab
Lower death rate and slower progression
Cardiac toxicity

Question 1

General Side effects of chemotherapy

Answer 1

Teratogenic, mutagenic, carcinogenic
Suppression of bone marrow activity
Reactions on skin and GI tract
Liver toxicity: alkylating agents and antimetsbolites
Neurotoxicity: plant alkaloids
Infection-immunosuppressive
Hemorrhage-toxicity to bone marrow decreased platelets

Question 2

Imantinib (gleevec)

Answer 2

Treats chronic myeloid leukemia
Tyrosine kinase inhibitor
Sustains remissions of CML
Toxicity: nausea, vomiting, diarrhea, edema, muscle cramps, rash, neutropenia, and thrmobocytopenia

Question 3

Gefitinib (iressa)

Answer 3

Used for non small cell lung cancer
Especially effective against tyrosine kinases associated with epidermal growth factor
Blocks growth signals mediated by tyrosine kinases
Only 10% have rapid response

Question 4

Bevacizumab (Avastin)

Answer 4

Tyrosine kinase inhibitor
Targets vascular endothelial growth factor
Inhibits angiogenesis

Question 5

Sunitinib (sutent)

Answer 5

Newer
Tyrosine kinase inhibitor
Targets vascular endothelial growth factor
Inhibits angiogenesis

Question 6

Sorafenib (nexavar)

Answer 6

Tyrosine kinase inhibitor
Targets vascular endothelial growth factor
Inhibits angiogenesis

Question 7

Suberoylanilide Hydroxamic Acid (vorinostat)

Answer 7

Treats epigentics
Histone deacetylase inhibitor
Acetylation of his tones maintain chromatin in an open transcriptionally active reading frame
Reactivate down regulate tumor suppressor genes inhibiting cell growth

Question 8

Azacytidine and Decitabine

Answer 8

Treat epigenetics
Inhibit methylation of DNA down regulating gene expression
Reactivate tumor suppressor genes inhibiting growth of cancer cells

Question 9

Methylguanine methyl transferase (MGMT) silencing

Answer 9

MGMT Repairs alkylation damage to DNA
Temozolomide is an alkylating agent
Alkylation maintains chromatin in open frame
Methylation decreases gene expression
Patients with methylated MGMT will be responsive to temozolomide treatment

Question 10

Dolastron (anzemet)

Palonosetron (aloxi)

Answer 10

Serotonin receptor antagonists
Prevention of nausea and vomiting due to chemo -increase compliance
Side effects: headaches, dizziness, diarrhea and constipation
P has a half life of 40 hours

Question 11

Dexamethasone

Answer 11

Corticosteroid
Serotonin receptor antagonist
Prevention of nausea and vomiting due to chemo-increase compliance
Side effects: headache, dizziness, diarrhea and constipation

Question 12

Chlorambucil

Answer 12

Non cycle active alkylating agent
Covalently modify DNA base
Oral absorption
Least toxic of alkylating agents
Used for chronic leukemias

Question 13

Cyclophosphamide

Answer 13

Non Cylce active alkylating agent
Covalently modifies DNA base
Requires metabolic liver activation
Liver toxicity and hair loss are side effects

Question 14

Carmustin (BCNU)

Answer 14

Non active cycle alkylating agent
Covalently modifies DNA bases
Lipid soluble-crosses BBB
CNS tumors

Question 15

Busulfan

Answer 15

Non cycle active alkylating agent
Covalently modifies DNA bases
Primarily used for myelosuppression
Relatively little GI tract toxicity

Question 16

Gemcitabine

Answer 16

Non cycle active alkylating agent
Inhibits DNA synthesis and alters DNA template activity
Effective against solid tumors

Question 17

Methotrexate

Answer 17

Cycle active antimetabolite
Folic acid analog
Parent compound is active
Renal excretion
DNA synthesis inhibitor-S phase
Decreases THF production
Binds to glutamate to become more water soluble and trapped inside cell-more sensitive
Do not administer in cases of renal impairment

Question 18

Folinic acid

Answer 18

Rescue methotrexate induced host toxicity in normal cells
Systemic
Decrease adverse reactions

Question 19

Mercaptopurine

Thioguanine

Answer 19

Cycle active antimetabolites
Metabolism is required to nucleotide mono phosphate level
Inhibit DNA synthesis-S phase
Inhibit multiple steps in purine synthesis

Question 20

5-fluorouracil

Cytarabine

Answer 20

Cycle active antimetabolites
Metabolism is required to nucleoside mono phosphate level
Pyramidine analogs, inhibit multiple steps in Pyramidine synthesis
5FU-hair loss
Folinic acid rescue

Question 21

Paclitaxel (taxol)

Answer 21

Natural product
Cycle active
Blocks mitosis

Question 22

Vincristine

Answer 22

Cycle active natural product
Vinca alkaloid
Inhibit mitosis, metaphase arrest 
Remission acute leukemia 
Minimal myelosuppression
CNS toxicity progressive and cumulative
Weakness, tremors, convulsions

Question 23

Vinblastine

Answer 23

Cycle active natural product
Vinca alkaloids
Inhibit mitosis, metaphase arrest 
Used for Solid tumors, Hodgkin's disease and testicular tumors 
Toxicity: is myelosuppression
Less neuro toxicity

Question 24

Etoposide

Answer 24

cycle active-s phase natural product
From mandrake plant
Inhibits topoisomerase causing DNA strand breaks
Used for Testicular cancer

Question 25

Topotecan

Answer 25

Cycle active natural product (s phase)
Topoisomerase inhibitor causing DNA strand breaks
Used for ovarian and lung cancer

Question 26

Actinomycin D

Answer 26

Non cycle active antibiotic
Inhibits RNA polymerase/RNA synthesis
Used for solid tumors
Very toxic especially bone marrow suppression

Question 27

Bleomycin

Answer 27

Non cycle active antibiotic
Mixture of related drugs 
Reacts with DNA-strand breaks
Used for solid tumors, testicular cancer and lymphomas
Pulmonary fibrosis occurs In 2-5%

Question 28

Doxorubicin (adriamycin)

Answer 28

Cycle active antibiotic
Inhibits topoisomerase 
Cardiac toxicity-arrythmias and congestive heart failure 
Loss of hair
Keep blood levels low and monitor

Question 29

Mitomycin

Answer 29

Non cycle active antibiotic
Alkylating agent
Used for solid tumors

Question 30

Prednisone

Answer 30

Corticoid

Induction of remission in leukemia

Question 31

Tamoxifen

Answer 31

Antiestrogen (estrogen drives cancer proliferation)
Metabolized in liver CYP2D6 to endoxifen the active form
Antidepressants (Paxil and Prozac) also metabolized by CYP2D6 causing decreased metabolism of tamoxifen

Question 32

Exemestane

Anastrozole

Answer 32

Aromatase inhibitors
Inhibit the metabolism of androstenedione to estrone which is then metabolized to estradiol
Decrease estrogen (estrogen drives cancer proliferation)
Treat many breast cancers that are estrogen receptor positive

Question 33

Flutamide + leuprolide

Answer 33

Antiandrogen
Leuprolide- analog of leurenizing hormone releasing hormone must be used or a bilateral castration-decrease synthesis and release of gonadotropins by pituitary
Blocks uptake of androgens
Used for metastic prostate cancer-May prolong life
Toxicity:gynecomastia, nausea and vomiting

Question 34

Cisplatin (oxaplatin, carboplatin)

Answer 34

MOA: similar to alkylating agents
Damages DNA
Non cycle active
IV administration
Excreted in urine
Toxicity: renal toxicity minimized by hydration, mannitol diuresis
Used for a variety if solid tumors: head/neck ovarian, bladder and testicular

Question 35

Hydroxyurea

Answer 35

Cycle active-S phase
Inhibits ribonucleotide reductase which Catalyzes the metabolism of ribonucleotidrs to deoxyribonucleotides
Inhibits DNA synthesis

Question 36

Mechanisms of cancer resistance

Answer 36

1. Inaccessibility of target site
   - catabolism of drug
   - decreased uptake
   - BBB-must be lipid soluble
2. Lack of metabolic activation by tumor
3. Target site becomes non critical
   - altered receptor
   - alternative metabolic pathway
   - precursor concentration overrides
   - long g1 less dividing