Oncology Antimetabolites Flashcards
Antimetabolites Mechanism (3)
Cell phase….
Structural analogs required for cell function and replication
Inhibits DNA synthesis via:
- Substitution for DNA base pair
- Or Inhibition of critical enzymes involved in DNA synthesis
S-phase specific
Antimetabolites
Folic acid analog 1
Methotrexate
Antimetabolites
Purine Analogs 2
6-mercatpopurine (6MP)
Nelarabine (Ara-G)
Antimetabolites
Pyrimidine analogues 3
5-Fluorouricil
Cytarabine (Ara-C)
Gemcitabine
Methotrexate is a…
dihydrofolate reductase inhibitor
Limits the denobale pathway for making the amino acid (thymidylate) that is important for making DNA; inhibiting DNA synthesis
Methotrexate IV doses (3)
Low dose
Intermediate dose (used in place of high dose for ALL patients with Down syndrome)
High dose (infusion from 4 – 24 hrs, followed by rescue folic acid analogue) • Give a lethal dose of methotrexate, wait 24 hours then give rescue of folic acid to treat the toxicity • Trying to flood the rapidly dividing cells and then give the rescue agent to go to the non-cancerous cells to bypass the system and help those cells stay alive
Capizzi dosing - Dose escalation based on patient tolerance
Methotrexate
PO and subcutaneous 3
- Low dose for non-oncologic uses
- Also used in cancer treatment usually during maintenance phase for ALL
- Go through intense phase and then maintenance phase
Methotrexate
Intrathecal (3)
All patients with ALL get IT chemotherapy with methotrexate
Can be given in combination with cytarabine
Dosing is fixed based on age
Methotrexate
Side Effects 8
- Myelosuppression
- Mucositis (especially with higher doses)
- N/V (less but do see with HD)
- Nephrotoxicity
- Hepatotoxicity
- Neurotoxicity (with HD, IT can cause seizures)
- Alopecia
- Photosensitivity: Counsel patients to wear sunscreen to prevent “MTX burns”
Methotrexate Special Considerations (2) 6 drug interactions
Avoid drug and food interactions, which can delay excretion!
- Bactrim, penicillins, tetracyclines, ASA, folic acid and NSAIDs
- Acid foods decrease excretion so until the drug is cleared patients should avoid super acidic drinks (i.e. cranberry juice, soda)
Patient with down syndrome are at higher risk of toxicities (i.e. more myelosupression, nausea/vomiting)
- They are also at higher risk for developing ALLA
• High Dose Methotrexate (3)
Doses range from…
Infusion times…
Doses range from 5 – 15 g/m2 depending on indication and protocol
Infusion times range from 4 – 24 hrs
Example 24 hr infusion:
12 g/m2
• 10% given as an IV bolus over 30 min
• 90% given over 23.5 hrs; protocol allows for up to 26 hrs for the infusion time
o MTX levels are drawn at
24 hrs
- If the infusion is over 24 hrs, the level is drawn immediately after the infusion has ended
- Bolus must be finished after 24h so that the level can be drawn
- Must be a peripheral stick for 1st level to avoid residual methotrexate in the line contaminating the results
Methotrexate Supportive Care (4)
- Requires leucovorin rescue by hour 42 or the dose is considered lethal
- If you don’t get it by hour 42 then it’s considered to be failed
- Leucovorin rescue is required
- Typically starts at hour 30 – 36 from the start of infusion
• 15 mg/m2 q6
Methotrexate
Things to think about(5)
- IVP or rapid infusion
- Maintain alkaline urine pH (> 7)
- Sodium bicarbonate should be in IV fluids
- IV hydration until MTX clears
- Avoid medications that can inhibit methotrexate excretion
MTX - Special Considerations
- Methotrexate needs to be protected from light
- When drawing labs, they need to be drawn in the dark and protected from light when sent to the lab
