Chemotherapy

Question 1

Chemotherapeutic agents are divided into …

Answer 1

Three classes

Class I - cycle nonspecific agents

Class II - phase specific agents

Class III - cycle specific agents

Question 2

Class I / cycle nonspecific agents are lethal in …

Answer 2

all phases of the cell cycle

Question 3

Class II / phase specific agents are lethal …

What do we know about their use/dose

Answer 3

exclusively or primarily during one phase of the cell cycle (usually S or M)

These drugs reach a plateau in cell killing with increasing dosages

Question 4

Class III / cycle specific agents are capable of …

Answer 4

damaging proliferating cells in various phases of the cell cycle

Question 5

Alkylating agents act by …

Answer 5

forming covalent bonds with the DNA and thus impeding DNA transcription and replication

Question 6

Why does dosing matter with the use of alkylating agents?

Answer 6

At low doses alkylating agents only affect cell in the cell cycle
–cycle specific

At high doses certain alkylating agents can act on cells in G0
–cycle non-specific

Question 7

Cyclophosphamide

• -type of drug
• -when should it not be used?
• -when is it indicated?
• -what is its unique toxicity?

Answer 7

Most commonly used alkylating agents

Not used in patients with liver deficiency

Indications: broad spectrum - including leukemia, lymphomas, and soft tissue cancers

Toxicity: hemorrhagic cystitis due to acrolein (a metabolite)

Question 8

What is Mensa?

Answer 8

A sulfhydryl reagent with “uroprotective” effect

Given with Cyclophosphamide or Ifosfamide to protect against hemorrhagic cystitis

Question 9

Nitroso-ureas

• -type of drug
• -unique feature
• -MOA
• -indications
• -toxicity

Answer 9

Alkylating agent

Liposoluble and thus go through BBB

They break down spontaneously to form alkylating and carbamoylating compounds – hence may inactivating DNA

Severe cumulative bone marrow depression

Question 10

Cytotoxic antibiotics act by ..

Toxicity?

Answer 10

Introduce breaks into DNA

Have a cumulative toxicity – so it is important to consider the total toxic dose

Question 11

Doxorubicine

• -effect mediated via
• -what is a benefit to this drug?
• -What is the unique toxicity of this drug?

Answer 11

Mediated via an effect on topoisomerase II – so this drug prevent religation meaning the DNA remains broken – this is toxic

Its a potent and broad-spectrum drug

Cumulative cardiotoxicity

Question 12

Belomycin

• -MOA
• -most effective when? (cell cycle)
• -toxicity

Answer 12

It belongs to a group of metal-chelating glycopeptide antibiotics that degrade DNA, causing chain fragmentation and release of free bases

Most effective in G2 and M phases. But may also act in G0

Total toxic dose is 300 mg / mm2
Triggers pulmonary fibrosis - so not given to pts with respiratory insufficiency

Question 13

Cisplatin

• -action
• -especially effective for ..
• -toxicity

Answer 13

Action similar to alkylating agents
Causes inter strand and intrastrand cross-linking

Especially effective in testicular and ovarian cancers

Toxicity

• serious nephrotoxicty
• GI distress

Question 14

What drugs are use as adjunctive therapy when treating with cisplatin?

Answer 14

5-HT3 antagonist antiemetics

Question 15

Oxaliplatin

–dosing

Answer 15

A dose schedule based on circadian rhythm seems to decrease adverse effects

Question 16

Methotrexate MOA

Answer 16

forms a stable complex with dihyrdofolate reductase and hence inhibits normal enzyme activity

Also prevents extracellular tetrahydrofolates from entering into the cell

Cell death seems to occur b/c of the inhibition of thymidylate synthesis (reaction 10x more sensitive to methotrexate than purine synthesis)

Question 17

Purine and pyrimidine analogs are effective…

Answer 17

because they are converted to fraudulent nucleotides

Question 18

Capecitabine is advantageous because..

Answer 18

it can be used as a single agent in metastatic breast cancers

Question 19

Etoposide MOA

Answer 19

induces stable DNA double strand breaks by inhibiting topoisomerase II activity

Question 20

Vinca alkaloids MOA

toxicity

Answer 20

Prevent MT growth by inhibiting tubulin polymerization. This effect affects mainly mitosis, but it also interferes with phagocytosis, chemotaxis, and axonal transport

These drugs are rapidly sequestered in WBCs and platelets

Toxicity - peripheral neurotoxicity

Question 21

Taxanes (Taxol)

• -importance
• -MOA
• -indications
• -toxicity

Answer 21

One of the most important break throughs in chemotherapeutic tx of advanced breast cancers toward the end of last century

Stabilize MT in the polymerized state

Indications

• breast cancer
• ovarian cancer

Toxicity - peripheral neuropathy

Question 22

Epothilones

–advantage?

Answer 22

compared to taxanes, they are

• -more amenable to synthetic modifications
• -poor substrates for p-glycoprotein
• -have high affinity to the various beta tubulin isoforms

Question 23

Tamoxifen

• -drug type
• -MOA
• -notable side effects

Answer 23

Antiestrogen

Selective estrogen receptor modulator (SERM)
Acts as a competitive receptor antagonist that prevents the transcription of estrogen responsive genes

LIFE THREATENING S/E!
Rapid resistance, stroke, venous thombosis, endometrial cancer

Question 24

Aromatase inhibitors

• -e.g.
• -MOA
• -s/e

Answer 24

Anastrozole

Block the final enzymatic step of estrogen synthesis

Decrease bone mass and increase fracture rate