WEEK 3: Treatment of cancer

Question 1

Why is chemotherapy administered in cycles?

Answer 1

Chemotherapy kills a constant fraction of tumor cells (first-order kinetics) rather than a constant number of cells (log kill hypothesis).

Question 2

Chemotherapy can target some of the common normal e rapidly proliferating cells result in the 4 main side effects.

State the 4 targeted rapidly proliferating cells and the symptom and side effects associated with that.

Answer 2

1. Hair follicles: Hair loss
2. GIT mucosa: GIT upset
3. Gonads: Infertility
   4.Bone marrow: Bone marrow suppression.

Question 3

State the 2 main types of traditional antineoplastic drugs.

Answer 3

• Cell cycle specific
• Non-cell cycle specific

Question 4

Cell specific drugs are more effective in tumors with high growth fraction.

State 2 examples.

Answer 4

*Leukemia
*Lymphoma

Question 5

S-Phase specific drugs are antimetabolites.

State the 3 drugs that target S-phase.

Answer 5

S-PHASE
 6 Mercaptopurine
 5 Fluorouracil
 Methotre

Question 6

Describe the MOA of 6 mercaptopurine.

Answer 6

1. Phosphoribosyl amine is a precursor to
   IMP (Inosonic acid)

 IMP Is the Immediate Precursor to GMP
(Guanylate) and AMP (Adenylate)

 AMP and GMP are purine nucleotides.

 6 mercaptopurine Inhibits DNA and
RNA synthesis

Question 7

6-mercaptourine is inactivated by __________________ (which is inhibited by
______________.)

Answer 7

6-mercaptourine is inactivated by xanthine oxidase (which is inhibited by allopurinol)

Question 8

Describe the MOA of 5 fluorouracil.

Answer 8

It is converted into a ‘fraudulent’ nucleotide fluorodeoxiuridene monophosphate which inhibits
thymidylate synthase and blocks DNA synthesis.

Question 9

State the 2 side effects of fluorouracil.

Answer 9

 Myelosuppression
 Gastrointestin

Question 10

 Folic acid analogue
 Inhibits dihydrofolate reductase and
blocks the formation of
tetrahydrofolate

SIDE EFFETCS
 Myelosuppression
 Nephrotoxicity

What drug is this?

Answer 10

Methotrexate

Question 11

Name the G2 phase specific drug.

Answer 11

Bleomycin.

Question 12

Describe MOA of Bleomycin.

Answer 12

 Metal chelating antibiotic that acts by induction of DNA strand breaks.

 Generates of superoxide and hydroxyl radicals

SIDE EFFECTS
 Myelosuppression is rare.
 The dose limiting adverse effect of the drug is pulmonary toxicity.

Question 13

Name the M phase specific drugs

Answer 13

1. Vinka alkaloids
2. Taxanes

Question 14

Describe the MOA of vinka alkaloids.

Answer 14

 Inhibit microtubule polymerization.

Question 15

State the 2 examples of vinka alkaloids and their side effects.

Answer 15

 Vincristine is neurotoxicity
 Vinblastine is myelosuppression.

Question 16

Descibe the MOA of taxanes.

Answer 16

 Taxanes promote microtubule polymerization.

Question 17

State the side effects of taxanes.

Answer 17

 Myelosuppression and peripheral neuropathy (Dose-limiting)
 Hypersensitivity (Premedicate with dexamethasone and H1

Question 18

State the 2 main characteristics of cell cycle non-specific drugs.

Answer 18

 Interact with DNA at all phases.
 Effective for both low-growth and high
growth tumors.

Question 19

State the 2 types of cell-cycle nonspecific drugs.

Answer 19

1. Alkylating agents
2. Antitumor antibiotics

Question 20

State the 3 examples of alkylating agents.

Answer 20

 Nitrogen mustards (cyclophosphamide)
 Nitrosoureas (lomustine, carmustine)
 Platinum compounds (cisplatin)

Question 21

Cyclophosphamide is a pro drug.
What activates it and where?

Describe MOA of cyclophosphamide.

Answer 21

 It is inactive until metabolized in the liver by the P450 mixed function oxidases.

 Phosphoramide cross-links DNA

Question 22

Name the metabolite of cyclophosphamide that causes hemorrhagic cystitis.

What is its antidote?

Answer 22

 Its metabolite called acrolein causes hemorrhagic cystitis.

Antidote is Mesna.

Question 23

Describe LOMUSTINE & CARMUSTINE

What tumors are they usually used to treat?

Answer 23

 Nitrosoureas
 Lipid soluble
 Used to treat tumors of the
brain and meninges

Question 24

 Low myelotoxicity
 Causes severe nausea and
vomiting (Ondansetron)
 Highly nephrotoxic (Amifostine)

What drug is this?

Answer 24

CISPLATIN

Question 25

What is an antibiotic?

Answer 25

An antibiotic is a chemical substance
produced by a living organism, generally a
microorganism, that is detrimental to other
organisms.

Question 26

Name the antitumor antibiotic.

Answer 26

Doxorubicin

Question 27

Describe MOA of doxorubicin.

Answer 27

 Intercalates into the DNA
 Inhibits DNA gyrase (Topoisomerase II)
 Generates free radicals that damage DNA.

Question 28

Doxorubicin is Cardiotoxic.

How does that come about?

Name the antidote and describe its MOA.

Answer 28

 Cardiotoxic: Antidote is an iron chelator DEXRAZOXANE (Blocks generation of free radicals)

Question 29

State the 3 types of targeted cancer chemotherapy.

Answer 29

 Steroid hormones and their antagonists
 Monoclonal antibodies
 Tyrosine kinase inhibitor

Question 30

Hormonal therapy table on notes.

Question 31

Describe the MOA of RITUXIMAB (MONOCLONAL ANTIBODY).

What is it used for treatment of?

State its adverse side effects.

Answer 31

 It is directed against the CD20 antigen that is found on the surfaces of lymphocytes.

 Treatment of leukemias and lymphomas
and rheumatoid arthritis.

 Adverse reactions include fever, chills,
hypotension, bronchospasms, and
angioedema

Question 32

Describe MOA of tyrosine kinase inhibitors.

Question 33

MECHANISMS OF RESISTANCE

Answer 33

 Spontaneous mutations of the target genes
 Amplification of target genes
 Overproduction of p-glycoproteins
 Induction of detoxification mechanisms
 Rapid DNA repair

Question 34

COMBINATION OF DRUGS

Answer 34

 Has more success than single drug treatment
 High response rates
 Decreased acquired resistance.
 Drugs with different toxicities are often combined.
 Therapy is scheduled intermittently to allow the body to recover a bit.