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SADL Oncology > Chemotherapy > Flashcards

Flashcards in Chemotherapy Deck (33):
1

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 

2

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.

3

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.

4

General toxicities of chemo

Myelosuppression
-Immunosuppression
-Nausea/Vomiting
-Mucositis
-Alopecia
-Allergic reactions
-Extravasation

5

Mechanism of Methotrexate action

Inhibits DHFR:
Inhibits synthesis of purines + thymidine
Both cytotoxic + immunosuppressive

6

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

7

Drugs that interact with methotrexate

PCP prophylaxis: Septra
Penicillins
Penems
PPIs
Fluoroquinolones
NSAIDs
Some macrolides
Acyclovir

8

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

9

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

10

TYPES OF ALKYLATORS

Nitrogen Mustards: cyclo, ifos, melphalan


Platinum compounds: cisplat, carbo, oxal


Nitrosureas: CCNU, BCNU


Others: Busulfan, Procarbazine, Dacarbazine, Thiotepa

11

Alkylators mechanism of action

Binding of alkyl group to DNA
Results in cross links –inter and intra strand ---> APOPTOSIS
Cell cycle NON SPECIFIC

12

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.

13

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

14

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

15

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

16

Dactino toxicity

Bleo toxicity

Dactino: emesis, myelosuppression, mucositis, extravasation, radiation recall. Veno-occlusive disease of the liver

 

Bleo: Not myelosuppressive. Skin toxicity, allergic reaction, fever, Raynaud's, Pulmonary toxicity

RF for pumonary toxicity: total dose over 450 U (in adults), renal insufficiency, younger age (<8y), older age (>30y), smoking, concurrent radiation or oxygen

17

VincaAlkaloids

- mechanisms of action

- toxicities

MECHANISMS: Arrest cell division by tubulin binding and inhibiting microtubule polymerization. Impaired mitotic spindle formation. Specific for M phase (metaphase)

TOXICITIES:

  • Neuropathy (constipation, jaw pain, foot drop, paraesthesia)
  • Minimal myelosuppression with vincristine, some with others
  • SIADH
  • Extravasation burn

18

Epipodophyllotoxins

- mechanism of actin

- side-effects

MECHANISM: Inhibit topoisomerase II, cell cycle specific for S and G2 phases

 

TOXICITIES

  • General: Myelosuppression
  • Acute: Allergic reactions (use Etopophos)
  • Chronic: Secondary leukemia – 11q23/MLL

19

Etoposide reactions: what are the next steps

  • stop infusion
  • treat anaphylaxis
  • If minor reaction can consider pre-treating and trying Etop again at slow rate
  • If major, switch to Etop-phos (needs SAP) with premeds

20

IrinotecanInduced Diarrhea

Immediate Onset
•Secondary to cholinergic properties
•Often accompanied by lacrimation, salivation, abdominal cramping, rhinitis
•Mean duration 30 minutes
•Responds to atropine
•If no response, treat as per delayed onset

Delayed Onset
•At >24 hours after exposure
•Predictors:
–Weekly administration
–Elevated Cr, Leukopenia
–Prior abdominopelvic RT
–Gilbert and Crigler-Najjarsyndrome
•Start loperamide at first sign
•Use octreotide if not controlled
•Cefpodoximeor cefixime for remainder of therapy* (to clear GI bacteria which convert SN38G back to active SN 38)

 

21

Rituximab side-effects

  • Infusional reactions –75% of patients; lessen with subsequent doses. Pre med w/ antihistamine, antipyretic
  • Transient hypotension. Slow infusion titrated up as tolerated over 4-6h
  • 5-10% risk of serum sickness
  • Hep B reactivation
  • B cell depletion –persistent x 6 months; no major infx
  • PML–progressive multifocal leukoencephalopathy; very rare (< 0.1%), JCvirus reactivationRituximab

22

Ch14.18

- target

- mechanism of action

- side-effects

Targets GD2 ganglioside

Mechanisms of action: Neutrophil + monocyte ADCC –augmented by GMCSF. Lymphocyte ADCC –augmented by IL-2. Complement activation

Side effects –significant infusionalreactions pain, fever, capillary leak, anaphylaxis

23

Pre-medications for Ch14.18

- Tylenol

- morphine

- Benadryl

- albumin

- ranitidine

- IV fluids

- consider hydroxyzine or certirizine

- consider gabapentin

24

Blinatumomab: BiTE

-mechanism of action

- administration

BiTE–bispecificT-cell engager. Molecule binds both CD19on B cells and CD3 on T cells. Kills by T cell cytotoxicity

Administration: Very short half life. Given by continuous infusion (over 4 weeks!)


Side effects: Infusional reactions, hypogamma, seizures, encephalopathy

25

Timing of different phases of emetogenicity

Acute: 1st dose of chemo. Last 24 hours post. 

  • Ondans/Granisteron, Dex, nabilone

Delayed: begins 24 hours after last dose. Lasts 7 d

  • Dex, metaclopramide

Anticipatory: occurs within 24h prior to first dose

  • Lorazepam

26

Which chemo requires extra hydration?

Ifos

Cyclo

Cisplat

MTX

27

Mucositis management

Oral care
–Good oral hygiene
–NaHCO3 mouthwash QID
–Avoid spicy, acidic, hard, hot foods

Pain control
–Low threshold for opioid analgesia
–Patients with moderate/severe symptoms may need morphine infusion

IV fluids +/-TPN

HSV prophylaxis +/-treatment

28

Determinants of CNS penetration

CNS blood flow

Drug properties: lipophilicity, molecular size, degree of ionization, free plasma concentration

29

Which chemos can be dialyzed?

Methotrexate

Platinum compounds

Oxazophorines

30

Which enzyme polymorphisms affect mercaptopurine metabolism?

TMPT

NUDT15

31

Which chemo causes SIADH?

Oxazophorines (Cyco/Ifos)

Vinca alkyloids

32

Carboplatin: Name 2 s/e not seen in Cisplat

Myelosuppression

Hypersensitivity reaction

33

Anthracycline mechanism of action

Intercalation of DNA

Topoisomerase II inhibition

Free radical damage