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PR4152 > IC5 cancer adjunct > Flashcards

IC5 cancer adjunct Flashcards

1
Q

CINV pathophysiology

A
  • Central pathway
    • CNS - delayed phase
    • Vomiting center –> vagus nerve –> release sub P –> bind to NK1 receptors on vagal efferent
  • Peripheral pathway
    • Gut– acute phase CINV
    • Enterochromaffin cell of GIT –> 5HT3 release –> vagal afferent 5HT3 receptor
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2
Q

types of CINV (based on onset)

A

Acute
* 1-2hrs after admin
* Peak within 5-6hr, resolve in 12-24hr

Delayed
* Peak onset 48-72hrs after chemo
* resolve after 1-3d
* 50-90% of highly emetogenic regimen

Breakthrough
* NV despite preventive therapy

Anticipatory
* Conditioned response
* a/w uncontrolled emesis prior chemo

Refractory
* N/V occurring during subsequent cycles of chemo when antiemetic prophylaxis or rescue therapy has failed in previous cycles

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3
Q

3 step method for antiemetic regimen

A

1) assess chemotherapy emetogenicity
2) assess pt risk factors
3) select antiemetic regimen

nk1, 5ht, dex, olan, DA

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4
Q

assess emetic risk of tx drugs (IV)

A

Highly emetic risk (>90% risk)

  • Combination chemo regimen (ANTHRACYCLINE+ CYCLOPHOSPHAMIDE)
  • Carboplatin AUC ≥4
  • Carmustine >250mg/mm3
  • cisplatin
  • cyclophosphamide > 1500 mg/m2
  • decarbazine
  • doxorubicin ≥60g/m2
  • epirubicin >90mg/m2
  • ifosfamide ≥2g/m2 per dose

Moderate emetic risk 30-90% freq
Low emetic risk 10-30% feq risk
Minimal emetic risk <10% freq of emesis

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5
Q

emetic risk % for IV and PO

A

[IV]
high emetic risk >90%
Moderate emetic risk >30-90% freq
Low emetic risk 10-30% feq risk
Minimal emetic risk <10% freq of emesis

[oral]
mod-high ≥30%
minimal - mod <30%

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6
Q

(ANTHRACYCLINE+ CYCLOPHOSPHAMIDE)

for CINV risk

A

ANTHRACYCLINE
- daunorubicin, doxorubicin, idarubicin and mitoxantrone

CYCLOPHOSPHAMIDE
- bendamustine, busulfan, carmustine, chlorambucil, ifosfamide, lomustine, melphalan, procarbazine, or temozolomide

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7
Q

assess pt emetic risk

A
  • Younger age <50yrs
  • F
  • Hx of (low prior chronic alcohol intake/ previous chemo induced emesis/ motion sickness/ pregnancy emesis)
  • Anxiety
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8
Q

anti-emetic combination for high risk

A
  • Acute, day 1: NK1 + 5HT3 + DEXA
    ○ +/- OLA
  • Delayed day 2: DEXA (d2-4), OLA (d2-4 if used on d1)
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9
Q

anti-emetic combination for moderate risk

A

Acute: 5HT3 + DEXA

Delayed: DEXA d2-3

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10
Q

anti-emetic combination for low risk

A

Acute: 5HT3 or DEXA or DOPA

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11
Q

multi-day regimen
for D1 HIGH, D2-3 LOW

A

porphy therapy for expected emetogenicity on each day of chemo admin

delayed prophy for 2-3day after completion of chemo stillable to cover for low risk emetogenic risk

eg: 3day regimen
1st day ACUTE + 2 day DELAYED

Antiemetics for Day 1 : PO Aprepitant 125mg , IV Dexa 8mg , IV Granisetron 1mg

Antiemetics for Day 2 and 3 : PO Aprepitant 80mg , IV Dexa 8mg

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12
Q

NK1 antagonist

A

aprepitant PO 125mg OD day 1, 80mg OD day 2, 3

Fosaprepitant (150mg IV), (e.g., casopitant, vestipitant, netupitant)

netupitant 300mg (combi)

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13
Q

NK1 antagonist MOA, place in therapy

A

MOA: Binds to NK1 receptor, prevent sub P from binding.
Attenuate vagal afferent signals and exert antiemeticc effect

acute, delayed CINV

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14
Q

combi NK1 + 5HT3 antagonist

A

(AKYNZEO) netupitant 300mg + palonosetron 0.5mg

PO 1 cap on day 1

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15
Q

NK1 AE, DDI

A

AE: fatigue, weakness, N, hiccups

DDI: steroid, warfarin, BZP, chemo (ifosfamide)

SWIB

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16
Q

5HT3 antagonist

A

IV/PO ondansetron 8-16mg OD day 1
* ondansetron 8mg day 2 onwards (max 16mg)

IV/PO granisetron 1mg OD day 1
* IV/PO 1mg OM day 2 onwards
* 10mg TD patch

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17
Q

5HT antagonist MOA, place

A

MOA: Block 5HT3 receptors peripherally in GIT and centrally in medulla

acute CINV

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18
Q

5HT AE, DDI

A

AE: Headache , constipation, QTc prolongation (BBW), SS

DDI: serotonin antagonist, tramadol, meds that affet heart rhythm sotalol, quinidine

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19
Q

dexamethasone dose

A

IV/PO 12mg OD day 1
8mg OD day 2 onwards

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20
Q

DEXA MOA, place

A

Unkown - May be activity in central NS

Acute and delayed CINV

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21
Q

DEXA SE

A

Transient elevation BGL, insomnia (dose earlier in evening), ANX, gastric upset

Less common: psychosis
- Esp in paeds
reactivation of ulcers
- Take after food

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22
Q

dopamine antagonist

A

IV/PO metoclopramide 10mg OD-TDS

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23
Q

DOPA MOA, place

A

MOA: Block dopamine receptors in chemoreceptor trigger zone
* Stimulate cholinergic activity in gut
* Incr gut motility
* Antagonism of peripheral 5HT3 receptors in intestine

place: acute (low emetogenic), breakthrough

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24
Q

DOPA SE, DDI

A

SE: Mild sedation, D, EPSE (dystonia, akathisia)

DDI: Avoid with olanzapine
* Incr EPSE (NMS, tardive dyskinesia)

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25
Q

Olanzapine dose and place

A

5-10mg OD (day 1-4)
consider lower dose 2.5mg OD for elderly

Acute and delayed CINV, (high emetogenic risk)

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26
Q

olanzapine MOA + SE

A

MOA: Antagonist of multiple receptors invovled in CINV
(DA, 5HT2, H, Ach)

SE: Fatigue, sedation, postural hypoTEN, Ach SE

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27
Q

adjunctive agents for refractory CINV

A

Place: not efficacious for upfront anti-emetic ACUTE or DELAYED CINV
○ May be used for refractory CINV

  • Butyrophenones (haloperidol APS)
  • Phenothiazines (prochlorperazine, chlorpromazine, promethazine)
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28
Q

Butyrophenones (haloperidol APS)

A

MOA: block DA receptors in CTZ
Dose: PO/IV 0.5-2mg Q4-6H
AE: sedate, EPSE

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29
Q

Phenothiazines (prochlorperazine, chlorpromazine, promethazine)

A

MOA: block DA receptors in CTZ
Dose: prochlor PO 10mg TDS/ QDS PRN
AE: drowsy, hypoTEN, akathisia, dystonia, EPSE

30
Q

breakthrough CINV

A
  • GIVE ADDITIONAL AGENT from a diff drug class
    ○ Choice based on assessment of current prevention strategies used
    ○ Use of several agents ultilising diff MOA if necessary
  • If PO not feasible (from NV), consider IV route
  • Hydration and fluuid repletion for losses
  • Reassess for NEXT cycle’s antiemetic to ensure regimen is appropriate
31
Q

anticipatory CINV

A
  • Prevention is key (optimal anti-emetic therapy DURING every cycle of tx)
  • Behavioural therapy
    ○ Relaxation, systematic desentisation
    ○ Hypnosis/ guided imagery
    ○ Music therapy
  • Acupuncture/ acupressure
  • BZP night before & 2-3hr before tx
32
Q

BZP dose and place

A

PO alprazolam 0.5mg-1mg
PO lorazepam 0.5 - 2mg (night before tx; 1-2hr before chemo)

Anticipatory CINV

Caution in elderly (risk of falls, use lowest effective dose)

33
Q

BZP MOA and SE

A

MOA: Binds to BZP receptors on postsynaptic GABA neuron to enhance inhibitory effect of GABA
* Lead to sedation
* Reduce ANX
* Possible depression of vomiting centre

SE: Drowsy, dizzy, hypoTEN, anterograde amnesia, PARADOXICAL RXN (hyperactive, aggressive)

34
Q

non-pharm for CINV

A
  • Take small freq meals, avoid heavy meals
  • Avoid greasy, spicy, VERY sweet/ salt food
    • Food with strong flavour/ smell
  • Sip small amount of fluids often > full glass
  • Avoid caffeinated beverages
  • Avoid lying flat for 2hrs after eating
35
Q

CID pathophysiology

A

Direct damage and inflammation to epithelial cells in mucosa of intestine, leading to imbalance between absorption and secretion

36
Q

potential CID causes by chemo tx

A

Targeted therapy: tyrosine kinase inhibitor, EGFRi
* PO targeted therapy
* Cisplatin/ oxaliplatin
* Cyclophosphamide
* Cytarabine
* 5FU/ capecitabine
* Gemcitabine
* Methotrexate
* Doxorubicin/ daunorubicin
* Taxanes
*Irinotecan/ topotecan

37
Q

pt risk factor for CID

A
  • Age >65yrs
  • Female
  • Eastern cooperative oncology group (ECOG) performance status (PS) of at least 2 – ambulatory, all DALY
  • Bowel inflammation or malabsorption
  • Bowel malignancy
  • Biliary obstruction
38
Q

CID predictive factor

A
  • First cycle of chemo
  • Cycle duration >3wks
  • Concomitant neutropenia
  • Sx of mucositis, NV, anorexia, anemia

MAAV

39
Q

Severity grading (Common Terminology Criteria for Adverse Events (CTCAE) version for CID)

A

Grade 1: Incr of <4 stools/d above baseline

Grade 2: limit ADLs
= Incr of 4-6 stools/day above baseline

Grade 3: hospitalisation needed, limiting self care
= Incr of ≥7 stools/d above baseline

Grade 4: life threatening = Urgent, intervention need
grade 5: death

40
Q

CID uncomplicated vs complicated

!!!!!!!
NSF CBD 2P

A

UNCOMPLICATED:
* Grade 1 or 2 + No complicating s&sx

COMPLICATED:
* Grade 3 or 4

  • Grade 1 or 2 w/ any of the 7 s&sx
    • Cramp
    • > grade 2 NV
    • Decr performance status
    • Fever
    • Sepsis, neutropenia
    • Frank bleeding (anus)
    • Dehydration
41
Q

goals of CID

A
  • Decr morbidity and mortality from CID
  • Improve QOL and ADL
  • Improve recover of intestinal mucosa
  • Decr hospitation
42
Q

uncomplicated CID tx

A
  1. Diet modifications
    • Oral hydration
  2. Withhold chemo for grade2
    • Resume when sx resolve
    • Dose reduction if needed
  3. Loperamide 4mg; 2mg Q4h/ after ep
    • Continue until 12h free of D
43
Q

uncomplicated CID progression after 12-24hr

A
  • Improve: continue with diet mod, begin solid foods
  • Persists: Lop 2mg BD
    ○ Add PO abx
    ○ (if lop not working) Octreotide/ 2nd line agent
  • Worsen severe/ complicated: tx as such
44
Q

complicated CID tx

A
  1. Withhold chemo (resume when sx resolve)
    • Restart at decr dose
  2. Administer
    • SC Octreotide 100-150mcg TDS
    • IV with dose escalation up to 500mcg TDS

IV fluid hydration
IV abx (ciprofloxacin x7d)

45
Q

loperamide dose and MOA

A
  • Dose: 4mg –> 2mg every 2-4hr/ after D
    Max 16mg/d
  • MOA: binds to u-opioid receptor in intestine, decr Ach
    Inhibit smooth muscle conc, decr motility
46
Q

LOP place and AE

A
  • Place: reduce fecal incontinence, freq of bowel movements and stool weight
  • AE: constipation, ab pain, dizzy, rash, bloat, NV, dry mouth, drowsy
    ○ High dose: paralytic ileus
47
Q

octreotide MOA

A

MOA: dcr hormone secretion, incr transit time within intestine, decr secretion of fluid and incr absorption of fluid and electrolytes

48
Q

octeotride dose

A
  • Dose: SC 100 - 150mcg TDS; IV 500mcg TDS; continuous IV infusion 25-50mcg/hr
    ○ May incr dose at 50mcg after 24h to 500mcg TDS
    ○ Dose-response r/s
49
Q

octreotide SE and place

A
  • AE: bradycardia, arrhythmia, NVC, ab pain, headache, dizzy, enlarged thyroid
  • Place: pt on 5FU and irinotecan
    ○ Resolution by day 3
50
Q

Irinotecan-associated diarrhea

A

Irinotecan –> SN38 (active metabolite) –> SN38G

SN38G –> SN38 (reactivated by gut bacteria)

  • early: 24h of admin, sx 30mins, dose dependent
  • late: after 24hr, onset 6d. any dose or freq
51
Q

early Irinotecan-associated diarrhea tx

A

SC/ IV Atropine 0.25-1mg (max 1.2mg)
○ MOA: Inhibit Ach at muscarinic receptor as competitive antagonist
○ AE: insomnia, dizzy, tachy, blurred vision, blurred mouth, C
○ CI: close angle glaucoma

52
Q

late Irinotecan-associated diarrhea tx

A

Loperamide 4mg –> 2mg Q2H/ 4mg Q4H (until 12h passed w/o bowel movement)

4+ (2x12) = 28mg. OR 4 + (4x6)=28mg
(vs usual max of 16mg)

53
Q

take note of medications for CID

A

Tyrosine kinase inhibitor
○ ~50% experience CID. Grade 3 CID in 30%
○ Dose dependent

Epidermal growth factor receptor inhibitors [subclass of TK proteins]
Incr EGFR in inflamed mucosa
○ Occur within 2-3d of therapy
○ Grade 3-4 diarrhea in <10%
○ Grade 2 in 20% for cetuximab, panitumumab
○ Grade 3 6-9%, any grade 60% for small-mole inhibitors (erlotinib, gefitinib, lapatinib)

Neratinib requires antidiarrheal prophylaxis with LOPERAMIDE for first 2 cycles

54
Q

non pharm for CID

A
  • Probiotics (Lactobacillus) prevent Chemo/ radiation induced D
  • Diet modifications
    • Avoid caffeine, alcohol, fruit juice, foods with lactose, spicy/ high fat food
    • Avoid high osmolarity fiber, dietary suppl
    • Avoid Lactose containing foods
      ○ Avoided at least 1 wk after CID resolved
      ○ 5FU induced lactose intolerance, as lactase activity lost temporarily
    • Eat small, freq meals
    • BRAT diet
    • Hydration 3L of clear fluids (salt, sugar, electrolyte)
55
Q

CIC pathophysiology

A

can cause dehydration
affect the nerve supply to the gut

56
Q

medication risk for CIC

A
  • Pain relievers: opioid narcotic (morphine, codeine)
  • Chemo: vinca alkaloids (vincristine vinblastine, vinorelbine)
  • AntiN drug (ondansetron, granisetron, anticonvulsant drugs)
57
Q

CIC risk factors

A
  • Low fluid intake and dehydration
  • LOA (anorexia)
  • Lack of fibre or bulk forming foods in diet
  • Vit or mineral suppl (Fe, Ca pills)
  • Overuse laxatives
  • Low PA/ lots of bed rest
  • Thyroid problems
  • Depression
  • High lvl of Ca/ K in blood
  • cancer growing into Large intestine or pressing on spinal cord
58
Q

sx of constipation

A
  • Bloat, feeling of fullness. Swollen/ distended abdomen
  • Cramp/ pain
  • Gas/ flatulence
  • Belching
  • LOA
  • No regular bowel movement for ≥2d
  • Straining bowel movement
  • Small hard stools, difficult to pass
  • Rectal P
  • Leakage of small amt of stool resembling D
  • NV
59
Q

PO tx for CIC

A
  • Stool softeners: macrogol (forlax 1 sachet BD)
    • Help stool hold water to keep it soft
  • Stimulant laxatives: senna 15mg ON, sennosides, mineral oil, lactulose 10ml TDS
    • Promote, stimulate bowel activity
  • Bulk forming laxative: Psyllium 1 sachet BD
    • incr fibre, bulk
60
Q

(not preferred) inserts for CIC

A

Inserts not recommended when WBC, PLT are low, risk of infection/ bleed

  • Suppositories: glycerine, bisacodyl
    • Promote bowel activity
  • Enema: phosphate enema (fleet), tap water
    • clean out bowel or deliver laxatives
61
Q

non pharm for CIC

A
  • More fibre
    • May not be advisable for CRC – large bulk
    • Prunes may not be advised – sugar
  • Natural laxatives
  • Incr PA (gravity)
  • Regular meals
62
Q

mucositis pathophysiology

A
  1. Cancer tx: damage to mucosa of oral cavity, pharynx, larynx, esophagus, GIT
  2. Chemo/ radiation: direct damage to epithelial stem cells
    • Targeted therapies: cetuximab, bevacizumab, rituximab, small mole inhibitors potential to cause GI toxicities
    • EGF role to maintain mucosal integrity. (EGFR found in esophagus, incr in inflamed mucosa)
    • Tissue response varies by seasonal and circadian changes
63
Q

pt risk factors for mucositis

A
  • Autoimmune factors
  • DM
  • Female (5-FU induced); Caucasian > african american
  • Folic acid of vit b12 deficiency
  • Genetic predisposition to tissue damage
    ○ Deficiency in genes produce enzymes responsible for metabolising chemo
64
Q

tx risk factors for mucositis

A
  • Chemo
    ○ Varies by agent and regimen
    ○ S-phase specific agents have highest risk
    ○ Duration, dose intensity, schedule
    ○ Prolonged or repetitive lower doses > risk > bolus doses
    ○ Incr with n.o. of cycles
    ○ CL of chemo delayed by renal/ hep impairment
    ○ Previous therapies toxic to mucosa
    ○ Previous ep of mucositis
  • Radiation (added to chemo)
    ○ Radiation source (throat area vs prostate), dosage, dose intensity, vol of mucosa irradiated
  • Smoking and alcohol
  • Xerostomia, infection
65
Q

mucositis grading

A
  • Grade 0: no evidence of mucositis
  • Grade 1: erythema, soreness
    ○ Asx or mild sx. No intervention
  • Grade 2: ulcer, eating solids
    ○ Mod pain; modified diet
  • Grade 3: ulcers, require lq diet
    ○ Severe pain, interfere with PO intake
  • Grade 4: ulcers, unable to take PO
    ○ Life threatening
  • Grade 5: Death
66
Q

mucositis progression with time

A

Day 0-5: asx, redness, swell, burn, incr sensitivity

Day 0-7: desquamation, white patches (mistaken for candidiasis)

Day 6-12: contiguous pseudomembranes

Day 7-16: painful erosions, ulceration

67
Q

goals for mucositis

A
  • Prevent or decr severity of mucositis
  • Manage pain and other associated sx
  • Prevent chemo delays or dosage reductions
68
Q

pharm to prevent oral mucositis

A
  • Palifermin $$$$$21,900/ box of 3vials
  • Benzydamine Hcl mouthwash
    ○ After radiation
  • Low level laser therapy.
    ○ After high dose chemo +/- TBI
  • Oral cryotherapy (ice chips)
    ○ After bolus 5FU
  • Oral hygiene
69
Q

Palifermin

A
  • Dose: IV 60mcg/kg/d x3doses BEFORE & AFTER tx
    ○ 6 doses (3 doses prior. 3rd dose 24-48hr before therapy. Last 3 doses start on same day as tx)
  • MOA: keratinocyte growth factor, reduce duration and severity of oral mucositis
  • Place: high dose chemo/ total body irradiation (TBI). Hematological malignancies (myelotoxic therapy, requiring HSCT)
70
Q

supportive care for mucositis (gargles)

A
  • Oracare susp (Nystatin 125,000U, tetracycline 62.5mg, hydrocortisone 5mg, diphenhydramine 11.5mg/10ml)
    ○ Antifungal, Abx, steroid (inflam), antihist (itch)
    ○ Swallow, after food to kill bacteria
  • Mylocaine susp (diphenhydramine 11.5mg, lignocaine 16.7mg/10ml)
    ○ Antihist (itch), pain relief
    ○ Can swallow Before food to reduce pain from swallowing
  • Morphine sulfate sol 1mg/ml
    ○ Swallow before food
71
Q

supportive care for mucositis (others)

A
  • Oracort-E: lidocaine, triamcinolone
  • Soregel: choline salicylate
  • Medijel: aminacrine (antiseptic), lidocaine
  • Difflam gargle/ spray: benzydamine
    * Alc as preservative, gargle and spit out
72
Q

non pharm for mucositis (mouthwash – gargle and spit out)

A

prevent dry mouth
Avoid alcohol based mouthwash (xerostomia –> mucositis)
* Oral 7 mouthwash: alc free, natural enzymes, neutral pH
* bioXtra mouthwash: natural enzymes, neutral pH

PR4152 (8 decks)

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