Chemotherapy

Question 1

What is the purpose of chemotherapy?

Answer 1

Chemotherapy is nothing
more than toxicity with a
purpose: get rid of the
target

Question 2

What is an ideal chemotherapeutic agent?

Answer 2

It is selectively toxic

Question 3

Log-kill effect

Answer 3

Drugs kill a constant fraction of cells
rather than a specific number

Question 4

Which normal cell populations are actively replicating?

Answer 4

e. g. blood, hair, skin, GI mucosa, pregnancy
* Toxicities occur because agents target these normal proliferating cells.*

Question 5

Give examples of chemotx drugs that are cell cycle specific.

Answer 5

• These inhibit or kill cells only if they are cycling (usually specific stage of cycle)*
• DNA synthesis inhibitors
• mitotic inhibitors

Question 6

Give examples of chemotx drugs that cell cycle non-specific.

Answer 6

• These work throughout the cell cycle*
• alkylating agents

Question 7

What are three reasons that drug resistance occurs?

Answer 7

1. Due to repetitive therapy
2. Acquired or innate
3. Mutation or gene expression

Question 8

Name 6 resistance mechanisms

Answer 8

Question 9

What is the MOA of methotrexate?

Answer 9

inhibits DNA synthesis by inhibiting
the synthesis of thymidine

MTX blocks DHFR and depletes the cell of tetrahydrofolate, THEREFORE Leads to DNA synthesis inhibition and inhibition of growth

Question 10

What are important ADME considerations for MTX?

Answer 10

absorption is dose dependent: low better absorbed than high

Question 11

Toxicities of MTX?

Answer 11

• Bone marrow and GI mucosa
• hepatoxicity with long term lo dose tx
• crystallizes in urine-renal damage

Question 12

Fluorouracil MOA?

Answer 12

Prodrug

FdUMP- inhibits _DNA _synthesis

FdUTP- inhibits _RNA _function

Also inhibits DNA synthesis by inhibiting the synthesis of thymidine >> Inhibits synthetic
enzyme: thymidylate synthetase

Question 13

Important ADME for fluorouracil?

Answer 13

Can use topically for actinic keratoses and non-invasive skin cancer.

IV also

RENAL metabolism and excretion

Question 14

Toxicities of fluorouracil?

Answer 14

• NV
• myelosuppression
• oral and GI ulceration

Question 15

Hydroxyurea uses

Answer 15

• leukemia
• radiation tx
• inducer of fetal hemoglobin in patients with sickle cell disease

Question 16

Hydroxyurea MOA

Answer 16

Inhibits ribonucleotide reductase

Enzyme converts ribonucleotides to the deoxy versions that are used to make DNA

In sickle cell, causes suppression of erythrocyte precursors and upregulation of promoters for HbF

Question 17

What is an important administration consideration with hydroxyurea in sickle cell disease?

Answer 17

Neutrophil counts should be maintained at least 2500 cells/mL

Question 18

Toxicities of hydroyurea?

Answer 18

Leukopenia, anemia and occasionally thrombocytopenia *does not increase secondary leukemia in sickle cell pt

• GI disturbances, mild dermatologic reactions
• Potent teratogen

Question 19

Cyclophosphamide MOA?

Answer 19

= alkylating agent - nitrogen mustard

Crosslinks DNA so that replication and transcription are impaired

• *Major lesion**: DNA-DNA crosslink
• *Minor lesions**: Damage to bases, DNA-protein crosslinks

Question 20

What are the metabolites of cyclophosphamide?

Answer 20

Metabolism is necessary for activity

Active metabolite: phosphoramide mustard

Toxic metabolite: acrolein

Question 21

Toxicities of cyclophosphamide?

Answer 21

• alopecia
• nausea, vomiting
• myelosuppression-dose limiting
• hemorrhagic cystitis-acrolein *ingest large amounts of fluid. MESNA-sulfhydryl reagent which deactivates
  acrolein