Chemotherapy Flashcards
High-dose methotrexate with CNS toxicity
- what are the stages?
- treatement options?
- early: hours/days, arachnoiditis
- subacute: days/weeks, encephalopathy
- chronic: months/years, progressive demyelinating encephalopathy
Treatment options:
- hold next IT
- leucovorin
- dextromethorphan
- hyperhydration
Vessicant/Irritant chemo and it’s management
- Vinca alkaloids: stop infusion, warm compress, hyaluronidase
- anthracycline: dexrazoxane/DMSO
- Dactinomycin:DMSO
- alkylating agents: sodium thiosulfate
Cold compress for: Anthracycline, antibiotics, alkylating agents
Warm compress for vinca alkaloids, taxanes, platin salts.
What is the Goldie Coldman hypothesis?
At any given time, a number of cells in a tumor are inherently drug resistant; this increases with tumor size. The best chance of cure is to use effective non-cross resistant chemotherapy in combination to maximize tumor kill.
General toxicities of chemo
Myelosuppression
- Immunosuppression
- Nausea/Vomiting
- Mucositis
- Alopecia
- Allergic reactions
- Extravasation
Mechanism of Methotrexate action
Inhibits DHFR:
Inhibits synthesis of purines + thymidine
Both cytotoxic + immunosuppressive
Methotrexate toxicity and management:
Primarily renal: related to drug concentrationand duration of exposure, myelosuppresion, mucositis, hepatic (elevated LFTs)
Mangement:
- hydration
- urinary alkalinization
- leukovorin
- measurement of levels
- carboxypeptidase (1U per 1uM MTX
Drugs that interact with methotrexate
PCP prophylaxis: Septra
Penicillins
Penems
PPIs
Fluoroquinolones
NSAIDs
Some macrolides
Acyclovir
6-MP
- mechanism
- metabolism
- toxicities
Incorporation into DNA as fradulentbase; Cytotoxicand immunosuppressive
Metabolized by TPMT -1/300 will have no functional TMPT –will need to use 25% of dose
TOXICITIES:
Early: rash, pancytopenia, stomatitis, oral lesions resembling thrush
Early/Delayed: hepatotoxicity(30%; 6TG>> 6MP), elevated LFTs
Cytarabine
- mechanism
- toxicities
Cytosine analogue, Cell cycle specific (S-phase)
Early: pancytopenia, fever, bowel necrosis, severe rash (<1%), conjunctivitis (use dexeye drops), nausea/vomiting with high dose
Cytarabine syndrome: flu-like syndrome 6-12 hours after IV cytarabine. Steroids as treatment + prophylaxis
Early/Delayed:neurotoxicity –onset at 5-7 days; cerebellar dysfunction, Sepsis –gram positive/strep viridans
TYPES OF ALKYLATORS
Nitrogen Mustards: cyclo, ifos, melphalan
Platinum compounds: cisplat, carbo, oxal
Nitrosureas: CCNU, BCNU
Others: Busulfan, Procarbazine, Dacarbazine, Thiotepa
Alkylators mechanism of action
Binding of alkyl group to DNA
Results in cross links –inter and intra strand —> APOPTOSIS
Cell cycle NON SPECIFIC
Oxazophorines
- acute side effects
1) Hemorrhagic cystitis: from accumulation of acrolein
- cyclo>1800, Ifos> 2000. Hydration and mesna
2) Nephrotoxicity: acute tubulopathy (ifos)
3) Neurotoxicity: Ifosphamide. 1-4d post. Somnolence, lethargy, hallucinations, coma, seizure. RF include renal/liver dysfunction, CNS rads, use of Cisplat. Treat with Methylene blue
Note: can be dialyzed
4) Cardiac: Cyclo >100mg/kg (BMT). within 14d, effusion, myocarditis, necrosis.
Oxazophorines
- long-term effects
1) Infertility: cyclo > 19g/m2, Ifos> 60g/m2, busulfan > 600mg/m2
2) Renal: Ifos related. RF: age<4, cisplat use, dose > 60g/m2
3) Secondary malignancy
Platinum compounds
- acute toxicity
- nephrotoxicity
–> hydration and salt loading protective for kidneys
- ototoxicity
- neurotoxicity: parasthesia, numbness, glove and stocking distribution (reversible sensory neuropathy)
- All less for carbo but it is more myelosuppresive
- emetogenic
Anthracyclines
- RF for cardiac toxicity
- protective agent
RF: age (younger gets more), chest rads, cumulative dose (>300mg/m2)
- Dexrazoxane. Increased risk of SMN in Hodgkin’s