Chemotherapy IV: Anti-metabolites

Question 1

Methotrexate MOA

Answer 1

Binds to dihydrofolate reductase decreasing tetrahydrofolate conversion from folic acid, causing cessation of nucleic acid synthesis

Cell cell specific (s phase)

Question 2

How does polyglutamation effect methotrexate?

Answer 2

Slows methotrexate exit from cell

Question 3

What can you administer to rescue the cell from cytotoxicity of methotrexate?

Answer 3

Tetrahydrofolate (leucovorin)

only if not polyglutamated!

Question 4

Methotrexate SE

Answer 4

Nausea, vomiting, stomatitis, myelosuppression

Question 5

In which patients should you dose reduce methotrexate?

Answer 5

Renal insufficiency

Question 6

Which drugs can you administer intrathecally?

Answer 6

Methotrexate, cytosine arabinoside (cytarabine)

Question 7

What color is methotrexate?

Answer 7

Yellow

Question 8

Methotrexate indication

Answer 8

Lymphoma, leukemia, brain tumors, breast cancer, rheumatoid arthritis, psoriasis

Question 9

Which drugs can potentiate the toxicity of Methotrexate and why?

Answer 9

ASPIRIN, PENICILLINS, SULFONAMIDES, PROBENECID

Aspirin, sulfonamides, penicillins (protein bound)

Aspirin, penicillins (all excreted in kidney as salt of weak acid- block excretion of MTX)

Probenecid blocks the organic acid transport system, interferes with excretion

Question 10

When is methotrexate contraindicated?

Answer 10

Ascites
Pleural effusions
Renal insufficiency

Question 11

How can you promote the excretion of Methotrexate?

Answer 11

Alkalinize urine (give IV or oral Na bicarbonate) >= 7 before administration

Question 12

Is methotrexate able to penetrate the CNS?

Answer 12

Yes at high doses- can provide protection to CNS against tumor spread

Question 13

How should methotrexate be administered?

Answer 13

• Alkalize urine (>7)
• High dose methotrexate (3-8 g/m2)
• IV/oral Leucovorin rescue (every 6 hours)
• Stop rescue when MTX is

Question 14

Pemetrexed MOA

Answer 14

Inhibition of thmidylate synthase

Question 15

Pemetrexed SE

Answer 15

MYELOSUPPRESSION = d-l

Rash, stomatitis, diarrhea, hand foot syndrome

Question 16

What can you pretreat with to prevent myelosuppression associated with Pemetrexed?

Answer 16

Vitamin B-12

Oral Folic Acid

Question 17

Pemetrexes Indication

Answer 17

Lung cancer

Mesothelioma

Question 18

Cytosine Arabinoside (cytarabine) MOA

Answer 18

Pyrimidine analog

Inhibits DNA polymerase and chain elongation

Question 19

Cytosine Arabinoside (cytarabine) SE

Answer 19

MYELOSUPRESSION

nausea, vomiting, hair loss, stomatitis, hepatic toxicity

Question 20

Cytosine Arabinoside (cytarabine) Indication

Answer 20

Leukemia (AML)

“cancer” meningitis

Question 21

Cytosine Arabinoside (cytarabine) has schedule dependent cytotoxicity, short half-life and is cell cycle specific… how should you administer?

Answer 21

3+ 7 regimen for AML

3 days of IV anthracycline

7 days of continuous cytosine arabinoside

Question 22

What are the SE of high dose cytosine arabinoside?

Answer 22

Myelosuppression, cerebellar toxicity, conjunctivitis

Question 23

What is an absolute indication to stop cytosine arabinoside?

Answer 23

cerebellar toxicity

Question 24

Gemcitabine SE

Answer 24

MYELOSUPPRESSION

Question 25

Gemcitabine Indication

Answer 25

Pancreas cancer

Lung cancer

Question 26

5- Fluorouracil MOA

Answer 26

Pyrimidine antagonist

S phase specific

Question 27

5- Fluorouracil SE

Answer 27

Nausea, vomiting, stomatitis, rash, diarrhea, and myelosuppresion

Hyperpigmentation of palms

Photosensitivity

Coronary artery vasospasm, cerebellar toxicity (rare)

Excess lacrimation, hand-foot syndrome

Question 28

What drug enhances the cytotoxicity of 5-FU?

Answer 28

Leucovorin

5-FDUMP + luecovorin form strong inhibitory complex with thymidylate synthase > thymineless death!

Question 29

What are the differences in effect of leucovorin on Methotrexate vs. 5-FU?

Answer 29

Leucovorin enhances the cytotoxicity of 5-FU and GI toxicity

Diminishes the toxicity/cytotoxicity of methotrexate

Question 30

What mutation can cause a patient to experience severe toxicity when given 5-FU?

Answer 30

Deficient in DPD (dihydropyrimidine dehydrogenase)

Autosomal recessive (3-5%)

Question 31

5-FU indication

Answer 31

breast, head, neck cancers
GASTROINTESTINAL CANCER

Radiation sensitizer (pancreas, rectal cancer)

Question 32

Capecitabine MOA

Answer 32

Prodrug of 5-FU (hydrolyze to active form by thymidine phosphorylase…more of this in tumor cells > normal cells!)

Question 33

Capecitabine Administration

Answer 33

ORAL!

Can replace IV 5-FU

Question 34

Capecitabine Indication

Answer 34

Gastrointestinal tract malignancies

Breast cancer

Question 35

Capecitabine SE

Answer 35

Rash
HAND FOOT SYNDROME
DIARRHEA
stomatitis

Question 36

6-Mercaptopurine MOA

Answer 36

Inhibits enzymes needed for purine nucleotide synthesis’

S-phase specific

Question 37

Which enzyme in the body will metabolize 6-Mercaptopurine to the inactive form?

Answer 37

Xanthine oxidase

Inhibited by allopurinol

Question 38

What should you do to the dose of 6-Mercaptopurine when co-administered with allopurinol?

Answer 38

Dose reduce 50-75%

Question 39

6-Mercaptopurine SE

Answer 39

MYELOSUPRESSION= d-l

Question 40

6-Mercaptopurine Indication

Answer 40

Childhood Leukemia

Question 41

6-thioguanine and allopurinol

Answer 41

Can be used at full dose because deamination does not involve xanthine oxidase