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BCOP- Joey > Toxicities > Flashcards

Toxicities Flashcards

1
Q

Diarrhea

A

-5FU, capecitabine
-irinotecan
-TKIs
-docetaxel, paclitaxel
-anti- EGGR
-sorafenib
-sunitinib
-mTOR inhibitors
-MTX
-Cytarabine
-ICIs

Irinotecan
-early onset (within 24h): IV/SQ atropine
-late onset (>24h): loperamide, IVF, or IR octreotide

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2
Q

Thrombocytopenia

A

-Carboplatin
-Gemcitabine
-mitomycin
-Procarbazine
-Vinorelbine

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3
Q

Hep B reactivation

A

CD-20 mAb (rituximab)
-per asco there is risk with all antineoplastics
- get hb surface antigen, anti-hb Core total, anti-hb surface total
-may need tenofovir or entecavir ppx

*consider antiviral ppx for HBsAg+ or HBcAb+

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4
Q

Hypersensitivity rxns

A

-platinums- occurs later in cycle (cycle 5+) d/t immune rxns
-taxanes- occurs early in cycle d/t solvent (paclitaxel has cremophor (Cremephor now called Kolliphor) and docetaxel has polysorbate 80)
-many mAbs
-fosaprepitant: polysorbate 80

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5
Q

Extravasation

A

-Doxorubicin and “rubicins” - cold compress, dexrazozane, DMSO
-dactinomycin- cold compress, DMSO
-meclorethamine- Cold compress, sodium thiosulfate, DMSO
-mitomycin- cold compress, DMSO
-trabectedin- cold compress
-vinca alkaloids: DRY warm compress, hyaluronidase
-Brentuximab vedotin
-ado-trastuzumab- cold compress
-taxanes (not nab-paclitaxel)-hyaluronidase

Others:
-carmustine
-mitoxantrone
-streptozocin
-teniposide (warm compress)
-cisplatin if > 20 mL of 0.5 mg/mL, (sodium thiosulfate)
-lurbinectedin
-trabectedin

Irritants:
Bendamustine-tx like Mechlorethamine
Oxaliplatin- warm compress
Etoposide- warm
Many others

-heat for non DNA binding but cold for DNA binding bc DNA binding isn’t neutralized/metabolized as it spreads, so it’ll just keep damaging tissue- so keep it in the same place
-DMSO 99% is topical- don’t use with dexrazoxane !!

DNA binding: anthracyclines, dactinomycin, mitomycin, mechlorethamine

Non-DNA binding: taxanes, vincas, Amsacrine, vindesine , trabectedin

-stop infusion, leave venous access device in place, elevate limb, aspirate drug, do NOT flush line, remove needle, compress

-if using dexrazoxane must start within 6 hours
-give antidote through a DIFFERENT venous access site (unless hyaluronidase)
-do NOT use DMSO with dexrazoxane

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6
Q

Electrolyte disturbances

A

-EGFR inhibitors- hypomag
-platinums- hypo: mag, ca, na, phos, k
-arsenic trioxide: hypo: k, mg, ca, also causes QTc prolongation
-FGFR inhibitors: hyperphos

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7
Q

Nephrotoxicity

A

-platinums
-cisplatin- pre and post hydration
-Carboplatin
-alkylating agents: cyclophosphamide, ifosfamide, bendamustine
-VEGF inhibitors: bevacizumab-proteinuria- need UA
-immune checkpoint inhibitors: immune mediated nephritis

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8
Q

Hemorrhagic cystitis

A

-HD cyclophosphamide
-ifosphamide

*give Mesna to bind acrolein
-other tricks: IVF, aminocaproic acid, Alum

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9
Q

Pulmonary toxicity

A

Interstitial infiltrates: bleomycin, MTX, taxanes, platinums, rituxan, gemzar, bortezomib, everolimus, temsirolimus, gefitinib

Diffuse alveolar damage: bleomycin, busulfan, carmustine, Melphalan, mitomycin, cyclophosphamide

Non-specific interstitial PNA: bleomycin, MTX, carmustine, chlorambucil

Pulmonary hemorrhage: HD cyclophosphamide, Cytarabine, mitomycin, bevacizumab, platinums

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10
Q

Dermatological toxicity

A

-immune checkpoint inhibitors
-EGFR inhibitors: cetuximab and panitumumab are notorious but this means better tx response

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11
Q

Ocular toxicity

A

-immune checkpoint inhibitors
-belantumab madofotin-off market
-tisotumab vedotin
-mivertuximab soravtansine

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12
Q

Neuropathy

A

-platinums
-taxanes-reversible
-Brentuximab vedotin or anything with “vedotin”
-ixabepilone
-bortezomib, carlfilzomib, ixazomib
-thalidomide, lenalidomide, pomalidomide- can be permanent

Treat with duloxetine, heat, or acupuncture. gabapentin or pregabalin are specifically not recommended (poor responses)
-note: duloxetine will help with pain but NOT numbness/tingling or cold sensitivity

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13
Q

Cold sensitivity

A

Oxaliplatin

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14
Q

Neurotoxicity

A

Ifosphamide- methylene blue is reversal agent, albumin for ppx, consider rechallenge if mild, change bolus to infusion, give inpatient next time

-vinca alkaloids- fatal, always give in minivan

-CAR-T, BiTEs, CD-19 mAbs- steroids, tocilizumab is reversal for cytokine release syndrome

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15
Q

Immune mediated ADRs

A

Nephritis, myocarditis, pancreatitis, pneumonitis, colitis, hepatitis, dermatitis

Weeks to occurrence
Derm: 2-3
Diarrhea: 6-7
Hepatitis: 8-12
Hypothyroid: 4-6
Hypophysitis: 8-9
Pulm: 12

Note: endocrine toxicity window never closes as most other tend to

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16
Q

Cardiotoxicity

A

-Anthracyclines: permanent
-HER-2 inhibitors: can be reversible
-checkpoint inhibitors: myocarditis
-5FU/capecitabine: vasospasms
-VEGF inhibitors: hemorrhage, VTE, HTN
-TKIs: QTC, arrhythmias

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17
Q

HTN

A

VEGF inhibitors, copanlisib, proteosome inhibitors, prostate drugs, RAF inhibitors, MEK inhibitors, ALK inhibitors

ESAs, NSAIDS, corticosteroids, trapiluspatercept

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18
Q

High emetogenic risk (<90%) IV

A

-anthracycline + cyclophosphamide
-carbo AUC >4
-carmustine >250 mg/m2
-doxorubicin >60 mg/m2
-Epirubicin >90 mg/m2
-cisplatin
-cyclophosphamide >1500 mg/m2
-Dacarbazine
-ifosfamide >2g/m2 per dose
-Mechlorethamine
-Melphalan >140 mg/m2
-fam-trastuzumab derutelan
-sactizumab govitecan
-streptozocin

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19
Q

Moderate to high emetogenic risk (PO)

A

-azacitadine
-busulfan >4 mg/ d
-ceritinib
-cyclophosphamide > 100 mg/d
-fedratinib
-lomustine
-midostaurin
-mitotane
-mobocertinib
-Selinexor
-Temozolomide >75 mg/m2/day

5HT3 RA daily + breakthrough

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20
Q

Emetogenic risk by radiation site

A

High: total body irradiation
Moderate: upper abdomen, craniospinal
Low: brain, head/neck, thorax, pelvis
Minimal: extremities, breast

High: 5HT3 + dex on day of RT and day after

Moderate: 5HT3 + dex on day of RT

Low and min: prn

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21
Q

Known risk of TdP

A

Vandetanib, Oxaliplatin, mobocertinib, arsenic trioxide

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22
Q

VEGFR

A

On target: HTN, hemorrhage, impaired wound healing, protenuria, thrombotic events

Other: hypothyroidism, dysphonia

Note: hx of VTE/MI, controlled HTN, being on anticoag are all NOt complete contraindications!

Hold all of these before procedures (even dental work)

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23
Q

BRAF

A

On target: dermatological, hand foot syndrome, rash, photosensitivity, non-melanoma skins cancers (less when given with MEK combo- same as with skin toxicity)

Fever -(more with combo) -onset 2-4 wks- more with BRAF/MEK combo): hold drug then resume at FULL dose once resolved—-> if no benefit with holding try prednisone 10 mg daily

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24
Q

RAF

A

On target: hand foot syndrome, rash

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25
Q

MEK

A

On target: none..?

Other: cardiomyopathy, fever, eye disorders

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26
Q

CDK 4/6

A

On target: myelosuppression, alopecia, nausea, mucositis

Other: pulmonary embolism, interstitial lung dx

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27
Q

EGFR

A

On target: rash, diarrhea, paronychia

Other: interstitial lung dx

USE SUNSCREEN

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28
Q

ALK and/ or ROS1

A

On target: bradycardia, visual disturbances

Other: interstitial lung dx, low-T (crizotinib), CNS toxicity (lorlatinib), increased CPK (Brigatinib, alectinib)

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29
Q

PARP inhibitors

A

-myelosuppression (especially anemia)
-less with Niraparib
-monitor CBC
-secondary leukemia/MDS
-Fatigue, GI

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30
Q

FGFR

A

On target: hyperphosphatemia

Other: eye disorders

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31
Q

HER-2

A

On target: LVEF dysfunction, diarrhea

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32
Q

RET

A

On target: hypothyroidism

Other: hypersensitivity (selpercatinib), QTc (Selpercatinib)

VEGF ADRs: HTN, impaired would healing, hepatotoxicity

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33
Q

MET

A

On target: Hepatotoxicity

Peripheral edema, hepatotoxicity, ILD

Capmatinib, tepotinib

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34
Q

NTRK

A

On target: CNS toxicity (including eye disorders), fractures

Other: edema

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35
Q

MTOR

A

On target: metabolic issues, impaired wound healing, infection, mucositis (NOT hand/foot syndrome)

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36
Q

PI3K-a

A

On target hyperglycemia , hepatotoxicity (need regular Liver function tests)

Other: pneumonitis

Diarrhea/ colitis (give budesonide or steroids), transient lymphocytosis, infections (CMV, PJP) from immunosuppression

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37
Q

FLT3

A

On target: myelosuppression

Differentiation syndrome

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38
Q

Which drugs cause Testicular hormonal dysfunction as well as ovarian issues and premature menopause ?

A

Alkylating agents, heavy metals (cisplatin/Carboplatin), Dacarbazine, TZM

-males lose gonadal function at lower cumulative doses than females
-pre-pubertal status of males at time of tx does not decrease risk
-older age (specifically 30+ in males) is a risk fx

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39
Q

Secondary AML, Myelodysplastic

A

<10 yr:Alkylating agents, heavy metals (cisplatin/ Carboplatin), Dacarbazine, Temozolomide, (ch 5 and 7 mutations) (MDS phase)

<5 yrs: anthracyclines, etoposide, teniposide (ch 11q23 mutation) (no MDS phase)

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40
Q

TLS high risk meds and dx states

A

-venetoclax, obinutuzumab, dinaciclib, alvociclib in sequential regimen with Cytarabine, mitoxantrone

High risk:
-AML- WBC >100k
-Burkitts bulky AND elevated LDH
-ALL- WBC >100k or LDH>2x ULN
-DLBCL bulky AND LDH >2x ULN

Intermediate
-Burkitts (normal LDH)
-DLBCL (non-bulky and LDH >2x ULN)
-HL bulky and LDH >2x ULN
-ALL WBC <100 and normal LDH
-CLL WBC >50 (unless venetoclax)
-AML WBC 25-100
-CML blast crisis
-germ cell, SCLC

Low risk
-multiple myeloma
-DLBCL non bulky and LDH<2x ULN
-solid tumors
-HL non-bulky and normal LDH
-all other CLL
-AML WBC <25k
-CML chronic or accelerated

Venetoclax high risk (admit to hospital for 1st dose of 20 and 40 mg, labs: pre dose, 4, 8, 12, 24hrs (for first two ramp ups) and pre dose, 6-8 and 24h for subsequent ramp ups
-ALC >25 AND any LN>5cm
-any LN>10 cm

Low (LN<5 cm, ALC <25) to mod risk (LN 5-10 cm OR ALC >25)
-labs: pre-dose, 6-8 and 24 hr (for 1st 2 ramp up) then pre dose at subsequent ramp ups

Note: all risks venetoclax requires at least PO hydration and allopurinol and blood chemistry monitoring, high risk needs IV and PO hydration + allopurinol + inpatient chemistry monitoring for first dose of 20 and 50 mg
High risk: also gets IV hydration and rasburicase if UA elevated
Note: normal LDH is 140-280

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41
Q

Tamoxifen vs AI toxicity and benefits

A

Tamoxifen
-less effective for post menopausal
-increases endometrial CA (post menopausal women)
-increase clotting
-increased BMD in post menopause (decreased in pre menopause)

AI
-more effective for post menopausal
-decreases BMD
-no risk for endometrial CA
-no risk for clots

Both:
-hot flashes
-myalgias/arthralgias

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42
Q

How to handle trastuzumab cardio toxicity

A

Hold, and rechallenge if EF recovers

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43
Q

Trastuzumab cardiotoxicity: monitoring and management

A

-Monitor BL and q3 months during tx and Q6 months after x2y

-hold x4 weeks if 16%+ drop in LVEF or if LVEF falls 10%+ and is below institution limits
-resume if LVEF normalizes in 4-8 weeks and is less than 15% decrease form BL

permanently stop if persists >8 weeks or if 3+ holds

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44
Q

Trastuzumab + pertuzumab cardiotoxicity: monitoring and management

A

-monitor BL and q3 months
-hold both x3weeks if:
-metastatic: LVEF <40% or 40-45% with fall of >10%
-(neo)adjuvant: LVEF <50% with fall of >10%
-resume if:
-metastatic: LVEF >45% or 40-45% with fall of <10%
-(neo)adjuvant: LVEF>50% or <10% below pretreatment value

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45
Q

Pericardial effusion

A

-cyclophosphamide
-Cytarabine
-dasatinib
-doxorubicin
-Gemcitabine

Treat with pericardiocentesis, pericardial window, subxiphoid pericardotomy, scleropathy of recurrent

Causes: lung, breast, leukemia/lymphoma, GI, sarcoma, melanoma

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46
Q

Which cdk 4/6 inhibitor increases QTc?

A

Ribociclib

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47
Q

When to d/c doxorubicin for cardio toxicity?

A

Decrease in LVEF of 10%+ to a level less than 50%

Note: get BL echo if risk fxs for CV dx and repeat within a year after tx completion

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48
Q

How often to get echo for traztuzumab?

A

-Q3 months during and upon completion
-Q6 months x2 years after completion

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49
Q

BTK inhibitor

A

Acalabrutinib: headache
Ibrutinib: cardiac- afib (don’t hold unless grade 3+), HTN, bleeding (risk greater in first 3-6 months)
Zanubrutinib: myelosuppression

All: lymphocytosis, diarrhea, infections, rash,
-arthralgias (big reason for discontinuation- don’t use NSAIDs), can hold x7 d then reduce dose
-diarrhea- give in evening, anti diarrhea agents
-myelosuppression, bleeding, afib, HTN,

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50
Q

BCR-ABl TKI comparison

A

imatinib
-fluid retention, nausea, rash, muscle cramps (tonic water or fluid w/ quinine, or calcium)
-with food

dasatinib
-fluid retention (pleural/pericardial effusions) (does NOT decrease over time like most ADRs), PAH, plt inhibition/bleed , avoid if pulmonary issues
-with or without food

nilotinib
-qtc prolongation, pancreatitis, peripheral arterial occlusive dx, metabolic syndrome
-BID so don’t use if poor adherence
-without food

bosutinib
-diarrhea, hepatotoxicity, avoid if GI issues
-with food

ponatinib
-ischemic rxns, arterial occlusion, HTN, pancreatitis, bleed risk,hepatotoxicity, heart failure, avoid if CV issues
-with or without food

asciminib
-well tolerated, asymptomatic amlylase or lipase elevation
-without food
-only one that doesn’t prolong QTc

Note: Ponatinib and dasatinib cross BBB the best

Hepatotoxicity: bosutinib, Ponatinib, nilotinib

Pancreatitis: Ponatinib, nilotinib

-all are 3A4 substrates
-imatinib and nilotinib are 3A4 and 2D6 inhibitors
-3 second gens avoid with acid suppressive therapy

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51
Q

Common ADR of “armed antibodies”

A

Thrombocytopenia

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52
Q

Minimal, Low, mod, high emetogenic risk definition

A

Minimal: <10%- acute
Low: 10-30%- acute
Moderate: 30-90%- acute and delayed
High: >90%- acute and delayed

53
Q

When to monitor echo for dox

A

-BL if risk fx
-250-300 mg/m2, 400 or 450 (if no risk fxs) mg/m2
-within a year after tx completion

54
Q

All TKIs

A

Diarrhea, rash, fatigue, transaminitis/hepatotoxicity, embyo-fetal toxicity

Possible slightly increased risk of developing other cancers

55
Q

CRS treatment

A

CAR-T
Grade 1: tocilizumab x1 if >3 days AND comorbidities/significant symptoms

Grade 2: tocilizumab (max 3/24h or 4 total) + steroid if persistent hypotension

Grade 3-4: tocilizumab + dex

Note: for idecabtagene and lisocabtagene consider dex 10 mg IV q24hr for early onset CRS (within 72 hr)

For Bispecific mabs (opposed to CAR-T
-Grade 1: supportive care
-Grade 2: monitor, steroids if needed
-Grade 3/4: steroids +/- tocilizumab

56
Q

PIK3a

A

Idelalisib, duvelisib

-autoimmune ADRshepatotoxicity (need regular Liver function tests) -diarrhea/colitis, pneumonitis,
-transient lymphocytosis, infections (CMV, PJP)
-diarrhea: lower grade ~first few weeks, severe ~9.5 months (give budesonide or steroids)

57
Q

CLL related toxicity’s/concerns

A

-infections
-autoimmune cytopenias (often with purine analogs)- give steroids
-ITP- use plt stimulating agents
-pure red cell aplasia treat with immunosuppressants
-TLS (esp bendamustine and venetoclax)
-non-melanomatous skin cancer (more likely to be aggressive and fatal than in non-CLL pts)

Others:
-may need viral and pjp ppx depending on therapy
-hep B screening
-vaccines may be less effective
-need flu, Covid, pneumococcal, and -recombinant zoster vaccine if tx naiive or tx with BTK-I
-avoid all live vaccine including live herpes zoster

58
Q

IMiD REMs requirements

A

Women
-2 forms BC or abstinence 4 weeks prior, during and 4 weeks after
-2 negative pregnancy tests (10-14 days before and within 24hrs before)
-weekly pregnancy tests in first month then monthly thereafter

Men
-condoms during and 4 weeks after (even if vasectomy)
-no donating sperm

Provider
-counseling
-confirming pregnancy tests
-max 28 day rx
-complete survey
-get auth# and write on rx along with pts risk category
-MD-patient agreement form and send to manufacturer
-send rx to certified pharmacy
-tell pt to do survey

Pharmacy
-obtain confirmation # from manufacturer and write on rx
-counsel pts /complete checklist
-dispense with medguide

59
Q

General grading of toxicity

A

Grade 1: annoying
Grade 2: affects ADLs
Grade 3: requires hospitalization
Grade 4: life threatening
Grade 5: death

60
Q

Management/ Rechallenge ICIs after IRAE

A

-grade 1: no need to stop (unless neurological, hematologic, cardiac)

-grade 2: hold until grade 1 or less, pred 0.5-1 mg/kg/d, ok to rechallenge

-grade 3: hold until grade 1 or less, pred 1-2 mg/kg/d taper over 4-6 wks, infliximab if no improvement in 48-72h, usually ok to rechallenge

-grade 4: permanently stop and no rechallenge (unless endocrine)

Notes:
-if using combo- downgrade to single agent PD-1 (not CTLA4)
-consider how long it took to resolve and if dx is stable or progressing
-dose reductions are generally NOT recommended upon resumption

61
Q

BRAF/MEK combo

A

-skin toxicity (but less than BRAF alone)
-Pyrexia (fever): hold and it should resolve, otherwise pred 10 mg QD - usual onset is 2-4 weeks in, median duration is 9 days (more with combo)

62
Q

IRAE: rash

A

Grade 1: <10% BSA. Continue tx. Topicals

Grade 2: 10-30% BSA (or >30% w/ mild/no symptoms) Consider holding or cont and monitor. Topicals, h1, steroid.

Grade 3: >30% BSA w/ mod-sev symptoms. Hold. Topicals, H1, high potency steroids, phototherapy?, may rechallenge

Grade 4: hospitalization/life threatening. Hold. Admit pt. Methylpred 1-2 mg/kg. Could possible rechallenge with close monitoring

63
Q

IRAE: colitis

A

Grade 1: <4 stools. Continue or hold until grade 1 or less. Monitor. Loperamide.

Grade 2: 4-6 stools. Hold until grade 1 or less. Pred 1 mg/kg/d taper 4-6 wks. Infliximab v vedolizumab. Consider permanent d/c ipilimumab

Grade 3: 7+ stools. Hospitalize. Electrolytes. Pred 1-2 mg/kg/d or methylpred. Infliximab or vedolizumab if symptoms cont 3+ days. Consider permanent d/c ipilimumab

Grade 4: life threatening. Follow g2-3 recs above. Methylpred 1-2 mg/kg/d. Infliximab or vedolizumab if inadequate response to steroid. Permanently d/c. (Ustekinumab or tofacitinib if refractory to others)

64
Q

IRAE: pneumonitis

A

Grade 1: asymptomatic, 1 lobe, <25% parenchyma. Hold. Monitor weekly. Resume of improvement. Tx as g2 if no improvement.

Grade 2: symptomatic, >1 lobe or 25-50% parenchyma. Hold until grade 1 or less. Pred 1-2 mg/kg/d taper over 4-6 wk. consider abx. Monitor q3d. If no improvement in 48-72h of pred tx as g3

Grade 3: severe symptoms. All lobes or >50% parenchyma. Hospitalize. O2. ABX. Methylpred iv 1-2 mg/kg/d- add infliximab if no improvements in 48h or mycophenolate or cyclophos or IVIG.
permanently discontinue

Grade 4: life threatening- intubation. Tx as grade 3 above.

Long steroid taper like hepatic

65
Q

IRAE: hypothyroidism

A

Grade 1: TSH 4.5-9.9 and no symptoms. Continue. Monitor TSH.

Grade 2: TSH persistently >10, moderate symptoms. May hold until symptoms resolve. Or continue and start Thyroid supplement for TSH>10.

Grade 3-4: severe symptoms. Life threatening. Hold until symptoms resolve. May admit for IV therapy like steroid. Thyroid supplementation.

66
Q

AI myalgias

A

-starts at ~6 weeks and can worsen over a year
-tx with duloxetine, acupuncture, Exercise
-change to another AI

67
Q

Which disease (and other risk fxs) have increased risk of rituximab infusion rxn

A

-CLL
-MCL

Note: even repeated severe infusion rxns do not necessarily preclude you from trying another appropriate mAb (e.g., obinutuzumab)

Other risk fxs:
-high cell counts
-pulmonary infiltrates
-elderly
-female

68
Q

Chemo induced oral mucositis

A

In order of increasing severity
1. Saline rinses, 2% viscous lidocaine rinse
2. Diet changes
3. Morphine 0.2% mouthwash
4. PCA

69
Q

RT induced oral mucositis

A

In order of increasing severity
1. Saline rinses, 2% viscous lidocaine rinse
2. gabapentin or low lvl laser therapy
3. Morphine 0.2% mouthwash
4. doxepin rinse
5. PCA

70
Q

Target therapy (everolimus/VEGF/TKI) induced oral mucositis “stomatitis”

A

In order of severity
1. Saline rinse
2. Dexamethasone mouthwash
3. Systemic corticosteroids

Notice no lidocaine or morphine rinse

71
Q

Gastrointestinal mucositis

A

Recommended
-Amifostine 340 mg/mg (prevent RT proctitis) in pts getting RT for rectal cancer
-octreotide 100 mcg SQ BID (diarrhea unresponsive to loperamide)

Suggestions
-Amifostine (esophagitis prevention)
-sucralfate enemas (RT Proctitis)
-sulfasalazine (RT enteropathy)
-lactobacillus probiotic (RT or chemo diarrhea)
-hyperbaric oxygen (RT proctitis)

72
Q

APL: When does differentiating syndrome usually occur?

Tx?

A

Median onset: 10-12 days

Tx: dex 10 Iv q12 x3-5d then taper x14d
-may need to also tx as empiric PNA

Continue therapy unless severe cardio respiratory symptoms

73
Q

General management of TKI toxicity

A

Grade 1-2: no change

Grade 3:
-first episode: dose interruption then restart at same dose
-second episode: reduce dose

Grade 3-4: consider permanent reduction or interruption

74
Q

What causes Pediatrics: growth hormone deficiency or metabolic syndrome/ obesity risk factors?

A

Head/brain/TBI

75
Q

Drugs that can cause radiation recall

A

-actinomycin
-bleomycin
-capecitabine
-5FU
-Cytarabine
-Gemcitabine
-pemetrexed
-MTX
-cisplatin
-Oxaliplatin
-cyclophosphamide
-Dacarbazine
-dactinomycin
-lomustine
-Melphalan
-daunorubicin
-doxorubicin (and liposomal)
-Epirubicin
-Idarubicin
-docetaxel
-paclitaxel (and albumin bound)
-Vinblastine
-Vinorelbine
-ixabepilone
-etoposide
-gefitinib
-sorafenib
-sunitinib
-interferon
-tamoxifen
-trastuzumab

76
Q

Radiation recall treatment

A

Skin reaction
Mild to moderate
-observation
-topical steroids, NSAIDS, antihistamines

Severe
-Stop or dose reduce
-High dose systemic steroids
-topical steroids, NSAIDS, antihistamines

Internal organs
Mild to moderate
-Stop or dose reduce
-High dose systemic steroids
-supportive care

Severe
-Discontinue
-High dose systemic steroids
-supportive care
-surgical consult as necessary

77
Q

IRAE: hepatic

A

Grade 2: hold. Pred 1-2 mg/kg/d
Grade and 4: permanently d/c. Systemic steroids- if no response in 2-3 days try adding mycophenolate mofetil or azathioprine. Do NOT use infliximab

Long steroid taper like pneumonitis

78
Q

Chemo induced diarrhea tx

A

Uncomplicated (Grade 1-2):
-non-pharm
-pharmacological tx
-hold chemo for grade 2
-if diarrhea persists after 24h of standard loperamide, increase to irinotecan doses loperamide
-if diarrhea persists after 48h or loperamide (or 24 hr of high dose loperamide) proceed to second line

Complicated (Grade 1-2 with other symptoms or 3-4):
-admit to hospital- IVF/electrolytes
-discontinue chemo
-octreotide- don’t stop abruptly (notice it’s first line for complicated)

Pharmacological tx
Loperamide
-4 mg -> 2 mg q4h (max 16 mg/day)
-irinotecan induced: 4 mg -> 2 mg q2h (max 24 mg/day)
-continue until 12h free of loose BM

Persistent
-octreotide 100-150 mcg SC TID (can increase up to 500 mcg, Or continuous infusion 25-50 mcg/hr- don’t stop abruptly
-tincture of opium

Other second line
-acute irinotecan induced: atopine (can give ppx or as tx
-diphenoxylate (+ atropine)
-budesonide
-absorbents
-probiotics

Grade 1: <4 stools/day over BL
Grade 2: 4-6 stools/day over BL
Grade 3: 7+ stools/day over BL

Can stop loperamide after diarrhea free for 12 hours, but for RT induced diarrhea continue throughout duration of RT

79
Q

EGFR papulopustular (acniform) rash

A

Pre-emptive (for at least first 6 wks of treatment)
-hydrocortisone 1% with moisturizer
-sunscreen
-doxycycline 100 mg BID (mino if high UV area-less photosensitizing)
-continue for first 6 weeks of treatment

Treatment
-initiate therapy that should’ve been used
-Grade 1: continue dose, topical hydrocortisone, topical clindamycin
-Grade 2: continue dose, topical hydrocortisone, PO doxy or minocycline
-Grade 3-4: Modify dose, topical hydrocortisone, PO doxy or minocycline, PO prednisone

Grading
-Grade 1: <10% BSA +/- symptoms
-Grade 2: 10-30% BSA, >30% without symptoms, psychosocial impact, limited instrumental ADLs
-Grade 3: >30% BSA with symptoms,
Limited ADLs: IV ABX indicated
-Grade 4: life threatening

Notes:
-usually within 2 weeks of initiation
-more common with mAbs that TKIs

80
Q

CLL lymphocytosis

A

Can occurs within first few weeks and last several weeks after tx initiation

Therapy should be continued!

-NOT ASSOCIATED WITH TLS OR LEUKOSTASIS
-slow resolution does not impact outcomes
-can happen with all kinase inhibitors used for CLL

81
Q

Pleurodesis

A

Used for pleural effusions- uses drugs to cause inflammation and adhesion between layers of pleura-this prevents fluid build up

Indicated after rapid re-accumulation of fluid following thoracentesis (so do THORACENTESIS FIRST)

Options (given intrapleural)
-Talc
-bleomycin (premed with APAP)
-doxycycline

Common with lung, breast, and lymphoma

Agents all cause pain

Chest tube is another option

82
Q

SVC syndrome

A

Causes: lung, lymphoma
Other: head/neck, breast, thymoma, germ cell

Treatment:
Surgery, chemo-RT (lymphoma, SCLC), stent, RT

83
Q

CINV

A

Acute: within 24h (peaks at 4-6h)

Delayed: >18-24h (peaks at 2-3d), can occur as late as 5 days
-cyclophos, ifosfamide, doxorubicin, Epirubicin, Carboplatin

Anticipatory

Breakthrough: N/V despite appropriate ppx regimen

Refractory: N/V despite optimal ppx and tx

Risk factors:
-prior CINV, anxiety/depression, decreased sleep night prior, children, women, <50y/o, non-drinker, motion sickness, morning sickness

84
Q

Capecitabine vs 5FU

A

Capecitabine has less stomatitis, alopecia, and neutropenia but MORE hand/foot syndrome and hyperbilirubinemia

85
Q

Hand foot syndrome and hand foot skin rxn

A

Hand foot syndrome:
-chemo (5FU/ capecitabine, etc)
-after 3-4 days
-Topical steroids don’t help

Hand foot skin rxn:
-TKIs (sorafenib, sunitinib, regorafenib etc)
-after 2-4 weeks
-Topical steroids help
_______________________________________
Prophylaxis
-ammonium lactate 12% cream BID or heavy moisturizer (petrolatum or lanolin based)
-diclofenac gel (hand foot syndrome)

Treatment
Grade 1:
-continue drug at current dose
-urea 20% cream BID AND clobetasol 0.05% daily
-reassess in two weeks

Grade 2:
-continue drug at current dose
-urea 20% cream BID AND clobetasol 0.05% daily AND NSAIDs/ gaba for pain
-reassess in 2 weeks and tx as grade 3 if not improved

Grade 3:
-Hold until grade 0-1
-clobetasol 0.05% daily AND NSAIDs/ gaba for pain
-reassess in 2 weeks and dose interrupt of stop if not better

Note: we always reassess in two weeks and step up to next grade if not improved

G1: redness,swelling, no pain
G2: bleeding, blistering, peeling, etc, limiting instrumental ADLs
G3: bleeding, blistering, peeling, etc, limiting self care ADLs THIS IS IMPORTANT BC DIFFERENTIATES WHEN WE HOLD THERAPY!!!

86
Q

Calcium levels to tx hypercalcemia

A

-<12 and no symptoms: don’t tx
-<12-14: tx esp if symptoms
->14 tx regardless of symptoms

87
Q

Radiation dermatitis

A

Prevention:
-keep clean and dry
-avoid sun/use sunscreen
-loose clothing
-don’t put on topicals before RT

Treatment:
Grade 1: no specific Tx, moisturizer

Grade 2-3: keep DRY, drying gels, hydrophilic dressings, zinc oxide, anti inflammatory emulsion, silver sulfadiazine, beta glucan, doxy is NOT recommended

Grade 4: wound care specialist

If co-occurring with EGFR rash- tx grade 1 like EGFR and grade 2+ like RT dermatitis

88
Q

ICANS tx

A

Grade 1: supportive care
Grade 2: dex x1- reassess in 6hr
Grade 3: dex 10 mg IV Q6h or MP 1mg/kg IV q12h. ICU care.
Grade 4: HD-steroids, ICU care, consider mechanical ventilation

Note:
-for idecabtagene and lisocabtagene if ICANS develops within 72hrs consider dex 10 mg IV q12-24hr x2 doses then reassess
-for Axicabtagene and brexucabtagene consider MP 1 gran QD x3-5d
-Axicabtagene consider ppx dex 10 mg PO QD x3 days

give keppra for seizure ppx with CAR-T cell therapy- usually happens a few weeks after CAR-T (start keppra day of therapy and continue x30 days after)

89
Q

Dex frequencies: ICANS, differentiation syndrome, CRS

A

ICANS: 10 mg IV q6h
CRS: x1 or unspecified
Differentiation: 10 mg IV BId x3-5d followed by 14 day taper

90
Q

Coasting

A

Ongoing neuropathy after stopping treatment

91
Q

CAPOX v FOLFOX

A

CAPOX is harder to tolerate

92
Q

Symptoms indicative of true hypersensitivity rxn as opposed to infusion rxn

A

Angioedema, urticaria, nasal congestion, dysphonia, wheezing

93
Q

Management of most BCR- ABl TKI toxicities

A

Hold until recovery then dose reduce

Sometimes discontinue if severe (PAH, clot)

Diarrhea maybe just hold until recovery

94
Q

Oxaliplatin vs cisplatin

A

Generally Oxaliplatin is better tolerated, but it does have more neuropathy

95
Q

Trastuzumab emtansine and deruxtecan cardiotoxic

Margetuxumab

A

Emtansine: basically tx the same as trastuzumab/Pertuzumab combo

Deruxtecan: hold for LVEF drop below 40% or >20% from BL or
If LVEF 40-45 and drop is 10-20% recheck it in 3 wks and permanently stop if not recovered

Margetuximab- Tx basically the same as trastuzumab

96
Q

Idecabtagene and ciltacabtagene REMS

A

For CRS and neurotoxicity (ICANS)

-healthcare facilities must be enrolled
-need at least 2 doses of tocilizumab available within 2 hours

97
Q

BITE REMS for teclistimab, elrantamab, talquetamab

A

CRS and neurological toxicities (ICANS)

-prescribers must certify by enrolling and completing training
-prescribers must counsel on CRS and neurotoxicity and provide pts with a wallet card
-pharmacies and healthcare facilities must be certified with REMS too

98
Q

IRAE hypophysitis

A

Pituitary dysfunction- Loss of cortisol, fails cortisol test

Give steroid

This is usually permanent!!

99
Q

Comparison of BRAF/MEK combo ADRs

A

Dabrafenib + trametinib: more fever and fatigue

Vemurafenib + Cobimetinib: more LFT elevation and skin rash / photosensitivity

Encorafenib + binimetinib: more CPK increase and LFT increase and nausea

Note: hold BRAF/MEK combo 1 day before and after stereotactic radiosurgery, and 3 days before and after fractionated radiation therapy

100
Q

FGFR inhibitor hyperphosphatemia management

A

-low phos diet
-phosphate lowering therapy if phos >7
-hold if phos >10 despite above interventions, or for mx episode of phos >7
-repeat phos is 1 week

101
Q

Targeted therapy with heart transplant

A

-HER-2 therapy ok since new healthy heart
-No ICIs d/t risk for organ rejection

102
Q

Prevention of hearing loss with cisplatin

A

-sodium thiosulfate: only if NON-metastatic hepatoblastoma

-don’t prolong infusion and don’t use Amifostine

103
Q

Why is albumin given with ifosphamide

A

Neurotoxicity prevention

104
Q

Venetoclax TLS monitoring and prevention

A

Venetoclax high risk (admit to hospital for 1st dose of 20 and 40 mg, labs: pre dose, 4, 8, 12, 24hrs (for first two ramp ups) and the outpatient pre dose, 6-8 and 24h for subsequent ramp ups
-ALC >25 AND any LN>5cm
-any LN>10 cm

Low (LN<5 cm, ALC >25) to mod risk (LN 5-10 cm OR ALC >25)
-labs: outpatient pre-dose, 6-8 and 24 hr (for 1st 2 ramp up) then pre dose at subsequent ramp ups

Note: all risks venetoclax requires at least PO hydration and allopurinol and blood chemistry monitoring, high risk needs IV and PO hydration + allopurinol + inpatient chemistry monitoring for first dose of 20 and 50 mg
High risk: also gets IV hydration and rasburicase if UA elevated

105
Q

Hypercalcemia of malignancy

A

-hydrate (+/- loop diuretics only after euvolemic), uop 100-150 mL/hr
-zolendronate 4 mg iv over 15 min or pamidronate 60-90 mg iv over 2-24h
-denosumab 120 mg sq weekly x3–>monthly- use if REFRACTORY to bisphosphonate. Benefit in 2-4d for both

-lymphoma and elevated vit D: pred 20-60 mg QD x10d or hydrocortisone 200 mg QD x3 d

-calcitonin 4-8 iu/kg SQ/IM NOT Nasal!! Q6-12h (alternate or adjunct to aggressive hydration. Dec 1-2 mg/dL in 4-6h. Efficacy limited to 48h

-calcimimetic if parathyroid carcinomas or hyperparathyroisism

-dialysis if renal insufficiency and can’t hydrate patient

106
Q

Mirvetuximab soravtansine vs tisotumab vedotin eye care

A

Mirvetuximab
Ocular toxicity - steroid eye drops day -1 x5d (6x/day)—>x4d (4x/d), lubricating drops; warm compress before sleep, sunglasses, no contact lenses

Tisotumab
-eye exam before each infusion
-steroid, vasoconstrictor, and lubricating eye drops
-ice packs during infusion

107
Q

ICI toxicity management via dose interruptions/dose adjustment

A

-dose interruption but don’t decrease dose after restarting

108
Q

Drugs that prolong QTc

A

ALK-Is: alectinib, Brigatinib, ceritinib, crizotinib
CDK4/6: Ribociclib
Vandetanib
Selpercatinib
Eribulin
Oxaliplatin
Sorafenib
Relugolix
Ivosidenib
Aresenic
Mobocertinib

Entrectinib
Pazopanib
Glasdegib
Dasatinib
Nilotinib
Dabrafenib
Vemurafenib
Toripalimab
Adagrasib
Osimertinib
Romidepsin
BCR-ABL tkis (especially nilotinib)
Gilteritinib
Lenvatinib
Sorafenib
Sunitinib
Midostaurin
EGFR: Erlotinib, gefitinib, afatinib, dacomitinib
Lapatinib

109
Q

Risk factors for CINV

A

Acute
-age </=40
-stage I-II
-anthra or platinum based
-non-rx drugs for n/v at home
-decreased risk with: age >40, GI/Gyn, comorbidities (cv, dm, GI/MSK/thyroid), etoh (>5 drinks/week), cycle 3+

Delayed
-age </=40
-prior cinv
-morning sickness
-current acute cinv
-decreased risk: more sleep night prior, cycle 3+

110
Q

CINV ppx

A

High Risk
-NK-1 + dex + 5HT3 + olz —> followed by olz 5-10 AND dex 8 on d2-4 (if AC just OLZ), aprepitant 80 d2-3 if used upfront
-could omit olz (not preferred)
-could do: palo + olz + dex

Moderate Risk
-dex + 5HT3 —> followed by either (not both) on d2-3
-could do palo + olz + dex
-could do NK-1 + dex + 5HT3 —> aprepitant 80 d2-3 (if used upfront) +/- dex d2-3

Low Risk
-dex 8-12 once or
-reglan 10-20 once or
-compazine 10 once or
-5HT3 once

Minimal Risk
-none- Breakthrough only

Oral chemo mod-high risk
-5HT3 daily
-min to low: PRN 5HT3, compazine, or reglan

Notes
-dex dose is 12 mg upfront, 8 mg for delayed
-zofran dose is 16-24 mg PO or 8-16 mg IV upfront and in delayed
-palonosetron dose is 0.5 mg IV
-granisetron dose is 10 mg sq, 2 mg po, 0.01 mg/kg IV, 3.1 mg for patch

111
Q

Cancer associated cacexia

A

-steroid: pred 10-20 mg BID or dex 3-8 mg/day
-megace 200-600 mg/day (VTE in 1/6 pts, and edema)
-olanzapine 2.5-5 mg daily

Conflicting results: reglan, Ritalin, dronabinol, marijuana, mirtazapine

112
Q

Other options for oral mucositis

A

-maalox in magic mouthwash can dry mouth and worsen mucositis
-no vasoline or petrolatum, increases bacterial growth
-no tooth whitening toothpaste

-cryotherapy for 5FU and HSCT
-benzydamine (not in us)
-palmiferin in auto HSCT heme ca + TBI and HD chemo
-low lvl laser therapy
-pca
-honey to prevent
-oral glutamine to prevent
-oral care protocols
-morphine 0.2% mouthwash

113
Q

Xerostomia

A

PPX
-adjust RT to spare salivary glands
-acupuncture
-bethanechol

Treatment
-topical lubricants and saliva substitutes
-sugar free lozenges or gum
-oral pilocarpine
-acupuncture
-transcutaneous electro stimulation

114
Q

RAI toxicities

A

Short term: n/v, dry mouth, dry eyes, taste changes, neck swelling and tenderness, salivary gland tenderness

Long term: low sperm count, irregular menstruation, Leukemia, gastric cancer, HNSCC

115
Q

Intravesical chemo

A

-Chemical cystitis (azo and anticholinergics)
-eczema desquamization- avoid urine contact/wash hands
-use condoms x48 hours

116
Q

Dexamethasone hiccups

A

Switch to methylprednisolone

Dex 8-12 mg —> MP 40-64 mg

117
Q

Taxane acute pain syndrome

A

Myalgias/arthralgias

Starts 24-48he after and lasts up to 7 days

118
Q

CAR-T new concern

A

T-cell malignancies

119
Q

Increased risk pulmonary toxicity with bleomycin

A

-40+ y/o
-GFR<80
-advanced dx
-cumulative dose >300 units
-prior hx lung disease
-smoking
-pulmonary irradiation

-Generally DLCO >60% is ok for giving bleomycin
-D/c if DLCO decreased >25%
-treatment is high dose steroids

120
Q

Acid suppressive therapy interactions

A

-Acalabrutinib capsules
-bosutinib, dasatinib, nilotinib
-erlotinib
-Pazopanib
-Selpercatinib
-sotorasib
-dacomitinib

-capecitabine
-gefitinib
-MTX (no PPI)
-Neratinib
-Pexidartinib
-sorafenib

121
Q

VegF monitoring for proteinuria

A

2+ on urine dipstick or >2 grams of urine protein on 24h urine collection

122
Q

Drugs with interactions with warfarin

A

-ibrutinib
-capecitabine
-5FU
-gefitinib
-erlotinib
-aprepitant
-TAMOXIFEN

All increase warfarin effect

123
Q

Management of neutropenia in Hodgkin’s lymphoma

A

-don’t reduce doses
-don’t use G-CSF (unless BEACOPP or Brentuximab vedotin)

124
Q

Hyperviscosity syndrome

A

-blood thickens- causes neurological symptoms, visual changes and mucosal bleeding
-oncologic emergency
-common in WM- don’t use rituxan if IgM is >4000
-pts often dehydrated and anemic
-Do NOT transfuse them
-give fluids, and plasmapheresis

-Worry sooner with AML than ALL cells are bigger (WBC >50k at AML but much higher with ALL)- size is also why we worry about CNS more with ALL bc smaller cells get in CNS easier
-leukopheresis

125
Q

When should you choose palonosetron over other?

Er SubQ granisetron?

A

If moderate emetogenic and not give with NK-1 or dex + olz

Granisetron er SubQ better if moderately emetogenic and not given NK-1

Otherwise they are all similar in efficacy

126
Q

Weight gain and loss

A

Gain: lorlatinib, alectinib

Loss: hedgehogs, talquetamab, axitinib, Cabozantinib

127
Q

Gnrh agonist ADRs

A

-hyperglycemia
-monit ecg and electrolytes

128
Q

Tamoxifen lipids

A

hypertriglyceridemia, DECREASES LDL/TC, inc HLD

129
Q

Hypersensitivity additional points

A

-if respiratory issues or hypotension (<90 or drop of 30+): anaphylaxis- give epi
-if pt on beta blocker may need to give glucagon if no response to 2 doses of epi
-NEVER rechallenge grade 3: hypoxia (O2<92), hypotension, neurologic compromise/confusion, collapse, loss of consciousness (mild respiratory symptoms ok) this is how I would handle taxanes

BCOP- Joey (11 decks)

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