Pharm Antineoplastic II, Folate Anti-metabolite

Question 1

*Methotrexate (MTX) MOA

Answer 1

• FOLIC ACID ANALOG
• MTX INHIBITS DHFR–blocks synthesis of thymidine, methionine and serine.
• Metabolite MTX(glu)n inhibits glycinamide ribonucleotide (GAR) and aminoimidazole carbozamide ribonucleotide (AICAR) transformylase–blocks synthesis of purines

Question 2

*Pemetrexed MOA

Answer 2

• Multiple Sites of action: Inhibitor of thymidylate synthase and GAR transformylase.
• MUCH less potent inhibition of DHFR compared to MTX.
• Can circumvent MTX resistance

Question 3

*Methotrexate High dose Therapeutic uses

Answer 3

• “Rescue WITH LEUCOVORIN”

- Prophylaxis with leukemia and high-risk lymphoma

Question 4

*Methotrexate Intermediate dose Therapeutic uses

Answer 4

• CHORIOCARCINOMA

- No agressive hydration, urinary alkalinization, or leucovorin rescue

Question 5

Methotrexate Low dose Therapeutic uses

Answer 5

• Intrathecal CNS prophylaxis
• IV for bladder/desmoid tumors
• Oral for ALL/APL

Question 6

*Pemetrexed Therapeutic Use

Answer 6

• PLEURAL MESOTHELIOMA (combo with cisplatin)

- Non-small cell lung cancer

Question 7

*Methotrexate Toxicity

Answer 7

• HIGH DOSE: REAL CRYSTALLURIA-RESCUE WITH LECUOVORIN
• GI PERFORATION
• Pregnancy Class D
• Bone Marrow suppression (thrombocytopenia, neutropenia)
• Mucositis

Question 8

Pemetrexed Toxicity

Answer 8

• Pregnancy Class D
• Bone Marrow suppression
• Caution in pts with even mild renal insufficiency/co-treatment with NSAIDs