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SADL Oncology > Chemotherapy > Flashcards

Chemotherapy Flashcards

1
Q

High-dose methotrexate with CNS toxicity

  • what are the stages?
  • treatement options?
A
  • early: hours/days, arachnoiditis
  • subacute: days/weeks, encephalopathy
  • chronic: months/years, progressive demyelinating encephalopathy

Treatment options:

  • hold next IT
  • leucovorin
  • dextromethorphan
  • hyperhydration
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2
Q

Vessicant/Irritant chemo and it’s management

A
  • 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.

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3
Q

What is the Goldie Coldman hypothesis?

A

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.

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4
Q

General toxicities of chemo

A

Myelosuppression

  • Immunosuppression
  • Nausea/Vomiting
  • Mucositis
  • Alopecia
  • Allergic reactions
  • Extravasation
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5
Q

Mechanism of Methotrexate action

A

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

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6
Q

Methotrexate toxicity and management:

A

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
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7
Q

Drugs that interact with methotrexate

A

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

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8
Q

6-MP

  • mechanism
  • metabolism
  • toxicities
A

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

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9
Q

Cytarabine

  • mechanism
  • toxicities
A

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

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10
Q

TYPES OF ALKYLATORS

A

Nitrogen Mustards: cyclo, ifos, melphalan

Platinum compounds: cisplat, carbo, oxal

Nitrosureas: CCNU, BCNU

Others: Busulfan, Procarbazine, Dacarbazine, Thiotepa

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11
Q

Alkylators mechanism of action

A

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

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12
Q

Oxazophorines

  • acute side effects
A

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.

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13
Q

Oxazophorines

  • long-term effects
A

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

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14
Q

Platinum compounds

  • acute toxicity
A
  • 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
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15
Q

Anthracyclines

  • RF for cardiac toxicity
  • protective agent
A

RF: age (younger gets more), chest rads, cumulative dose (>300mg/m2)

  • Dexrazoxane. Increased risk of SMN in Hodgkin’s
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16
Q

Dactino toxicity

Bleo toxicity

A

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
Q

VincaAlkaloids

  • mechanisms of action
  • toxicities
A

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
Q

Epipodophyllotoxins

  • mechanism of actin
  • side-effects
A

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
Q

Etoposide reactions: what are the next steps

A
  • 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
Q

IrinotecanInduced Diarrhea

A

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
Q

Rituximab side-effects

A
  • 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
Q

Ch14.18

  • target
  • mechanism of action
  • side-effects
A

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
Q

Pre-medications for Ch14.18

A
  • Tylenol
  • morphine
  • Benadryl
  • albumin
  • ranitidine
  • IV fluids
  • consider hydroxyzine or certirizine
  • consider gabapentin
24
Q

Blinatumomab: BiTE

  • mechanism of action
  • administration
A

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
Q

Timing of different phases of emetogenicity

A

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
Q

Which chemo requires extra hydration?

A

Ifos

Cyclo

Cisplat

MTX

27
Q

Mucositis management

A

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
Q

Determinants of CNS penetration

A

CNS blood flow

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

29
Q

Which chemos can be dialyzed?

A

Methotrexate

Platinum compounds

Oxazophorines

30
Q

Which enzyme polymorphisms affect mercaptopurine metabolism?

A

TMPT

NUDT15

31
Q

Which chemo causes SIADH?

A

Oxazophorines (Cyco/Ifos)

Vinca alkyloids

32
Q

Carboplatin: Name 2 s/e not seen in Cisplat

A

Myelosuppression

Hypersensitivity reaction

33
Q

Anthracycline mechanism of action

A

Intercalation of DNA

Topoisomerase II inhibition

Free radical damage

SADL Oncology (17 decks)

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