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
2
Q
Thrombocytopenia
A
-Carboplatin
-Gemcitabine
-mitomycin
-Procarbazine
-Vinorelbine
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+
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
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
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
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
8
Q
Hemorrhagic cystitis
A
-HD cyclophosphamide
-ifosphamide
*give Mesna to bind acrolein
-other tricks: IVF, aminocaproic acid, Alum
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
10
Q
Dermatological toxicity
A
-immune checkpoint inhibitors
-EGFR inhibitors: cetuximab and panitumumab are notorious but this means better tx response
11
Q
Ocular toxicity
A
-immune checkpoint inhibitors
-belantumab madofotin-off market
-tisotumab vedotin
-mivertuximab soravtansine
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
13
Q
Cold sensitivity
A
Oxaliplatin
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
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
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
17
Q
HTN
A
VEGF inhibitors, copanlisib, proteosome inhibitors, prostate drugs, RAF inhibitors, MEK inhibitors, ALK inhibitors
ESAs, NSAIDS, corticosteroids, trapiluspatercept
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
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
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
21
Q
Known risk of TdP
A
Vandetanib, Oxaliplatin, mobocertinib, arsenic trioxide
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)
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
24
Q
RAF
A
On target: hand foot syndrome, rash
25
MEK
On target: none..?
Other: cardiomyopathy, fever, eye disorders
26
CDK 4/6
On target: myelosuppression, alopecia, nausea, mucositis
Other: pulmonary embolism, **interstitial lung dx**
27
EGFR
On target: rash, diarrhea, paronychia
Other: ***interstitial lung dx***
***USE SUNSCREEN***
28
ALK and/ or ROS1
On target: bradycardia, visual disturbances
Other: interstitial lung dx, low-T (crizotinib), CNS toxicity (lorlatinib), increased CPK (Brigatinib, alectinib)
29
PARP inhibitors
-myelosuppression (especially anemia)
-less with Niraparib
-monitor CBC
-secondary leukemia/MDS
-Fatigue, GI
30
FGFR
On target: hyperphosphatemia
Other: eye disorders
31
HER-2
On target: LVEF dysfunction, diarrhea
32
RET
On target: hypothyroidism
Other: hypersensitivity (selpercatinib), QTc (Selpercatinib)
VEGF ADRs: HTN, impaired would healing, hepatotoxicity
33
MET
On target: Hepatotoxicity
***Peripheral edema***, hepatotoxicity, ILD
Capmatinib, tepotinib
34
NTRK
On target: CNS toxicity (including eye disorders), fractures
Other: edema
35
MTOR
On target: metabolic issues, impaired wound healing, infection, mucositis ***(NOT hand/foot syndrome)***
36
PI3K-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
37
FLT3
On target: myelosuppression
Differentiation syndrome
38
Which drugs cause Testicular hormonal dysfunction as well as ovarian issues and premature menopause ?
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
39
Secondary AML, Myelodysplastic
<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)
40
TLS high risk meds and dx states
-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***
41
Tamoxifen vs AI toxicity and benefits
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
42
How to handle trastuzumab cardio toxicity
Hold, and rechallenge if EF recovers
43
Trastuzumab cardiotoxicity: monitoring and management
-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***
44
Trastuzumab + pertuzumab cardiotoxicity: monitoring and management
-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
45
Pericardial effusion
-cyclophosphamide
-Cytarabine
-dasatinib
-doxorubicin
-Gemcitabine
Treat with pericardiocentesis, pericardial window, subxiphoid pericardotomy, scleropathy of recurrent
Causes: lung, breast, leukemia/lymphoma, GI, sarcoma, melanoma
46
Which cdk 4/6 inhibitor increases QTc?
Ribociclib
47
When to d/c doxorubicin for cardio toxicity?
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
48
How often to get echo for traztuzumab?
-Q3 months during and upon completion
-Q6 months x2 years after completion
49
BTK inhibitor
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,
50
BCR-ABl TKI comparison
***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
51
Common ADR of “armed antibodies”
Thrombocytopenia
52
Minimal, Low, mod, high emetogenic risk definition
Minimal: <10%- acute
Low: 10-30%- acute
Moderate: 30-90%- acute ***and delayed***
High: >90%- acute ***and delayed***
53
When to monitor echo for dox
-BL ***if risk fx***
-250-300 mg/m2, 400 or 450 (if no risk fxs) mg/m2
-within a year after tx completion
54
All TKIs
Diarrhea, rash, fatigue, transaminitis/hepatotoxicity, embyo-fetal toxicity
Possible slightly increased risk of developing other cancers
55
CRS treatment
***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
PIK3a
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
CLL related toxicity’s/concerns
-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
IMiD REMs requirements
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
General grading of toxicity
Grade 1: annoying
Grade 2: affects ADLs
Grade 3: requires hospitalization
Grade 4: life threatening
Grade 5: death
60
Management/ Rechallenge ICIs after IRAE
-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
BRAF/MEK combo
-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
IRAE: rash
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
IRAE: colitis
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
IRAE: pneumonitis
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
IRAE: hypothyroidism
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
AI myalgias
-starts at ~6 ***weeks*** and can worsen over a year
-tx with duloxetine, acupuncture, Exercise
-change to another AI
67
Which disease (and other risk fxs) have increased risk of rituximab infusion rxn
-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
Chemo induced ***oral*** mucositis
In order of increasing severity
1. Saline rinses, 2% viscous lidocaine rinse
2. Diet changes
3. Morphine ***0.2%*** mouthwash
4. PCA
69
RT induced ***oral*** mucositis
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
Target therapy (everolimus/VEGF/TKI) induced ***oral*** mucositis “stomatitis”
In order of severity
1. Saline rinse
2. Dexamethasone mouthwash
3. Systemic corticosteroids
***Notice no lidocaine or morphine rinse***
71
Gastrointestinal mucositis
***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
APL: When does differentiating syndrome usually occur?
Tx?
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
General management of TKI toxicity
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
What causes Pediatrics: growth hormone deficiency or metabolic syndrome/ obesity risk factors?
Head/brain/TBI
75
Drugs that can cause radiation recall
-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
Radiation recall treatment
***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
IRAE: hepatic
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
Chemo induced diarrhea tx
***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
EGFR papulopustular (acniform) rash
***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
CLL lymphocytosis
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
Pleurodesis
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
SVC syndrome
Causes: lung, lymphoma
Other: head/neck, breast, thymoma, germ cell
Treatment:
Surgery, chemo-RT (lymphoma, SCLC), stent, RT
83
CINV
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
Capecitabine vs 5FU
Capecitabine has less stomatitis, alopecia, and ***neutropenia*** but MORE hand/foot syndrome and hyperbilirubinemia
85
Hand foot syndrome and hand foot skin rxn
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
Calcium levels to tx hypercalcemia
-<12 and no symptoms: don’t tx
-<12-14: tx esp if symptoms
->14 tx regardless of symptoms
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Radiation dermatitis
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
ICANS tx
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
Dex frequencies: ICANS, differentiation syndrome, CRS
ICANS: 10 mg IV q6h
CRS: x1 or unspecified
Differentiation: 10 mg IV BId x3-5d followed by 14 day taper
90
Coasting
Ongoing neuropathy after stopping treatment
91
CAPOX v FOLFOX
CAPOX is harder to tolerate
92
Symptoms indicative of true hypersensitivity rxn as opposed to infusion rxn
Angioedema, urticaria, nasal congestion, dysphonia, wheezing
93
Management of most BCR- ABl TKI toxicities
Hold until recovery then dose reduce
Sometimes discontinue if severe (PAH, clot)
Diarrhea maybe just hold until recovery
94
Oxaliplatin vs cisplatin
Generally Oxaliplatin is better tolerated, but it does have more neuropathy
95
Trastuzumab emtansine and deruxtecan cardiotoxic
Margetuxumab
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
Idecabtagene and ciltacabtagene REMS
For CRS and neurotoxicity (ICANS)
-healthcare facilities must be enrolled
-need at least ***2 doses*** of tocilizumab available within ***2 hours***
97
BITE REMS for teclistimab, elrantamab, talquetamab
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
IRAE hypophysitis
Pituitary dysfunction- Loss of cortisol, fails cortisol test
Give steroid
***This is usually permanent!!***
99
Comparison of BRAF/MEK combo ADRs
***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
FGFR inhibitor hyperphosphatemia management
-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
Targeted therapy with heart transplant
-HER-2 therapy ok since new healthy heart
-No ICIs d/t risk for organ rejection
102
Prevention of hearing loss with cisplatin
-sodium thiosulfate: only if NON-metastatic hepatoblastoma
-don’t prolong infusion and don’t use Amifostine
103
Why is albumin given with ifosphamide
Neurotoxicity prevention
104
Venetoclax TLS monitoring and prevention
***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
Hypercalcemia of malignancy
-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
Mirvetuximab soravtansine vs tisotumab vedotin eye care
***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
ICI toxicity management via dose interruptions/dose adjustment
-dose interruption but don’t decrease dose after restarting
108
Drugs that prolong QTc
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
Risk factors for CINV
Acute
-age 40, GI/Gyn, comorbidities (cv, dm, GI/MSK/thyroid), etoh ***(>5 drinks/week)***, cycle 3+
Delayed
-age
110
CINV ppx
***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
Cancer associated cacexia
-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
Other options for oral mucositis
-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
Xerostomia
***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
RAI toxicities
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
Intravesical chemo
-Chemical cystitis (azo and anticholinergics)
-eczema desquamization- avoid urine contact/wash hands
-use condoms x48 hours
116
Dexamethasone hiccups
Switch to methylprednisolone
Dex 8-12 mg —> MP 40-64 mg
117
Taxane acute pain syndrome
Myalgias/arthralgias
Starts 24-48he after and lasts up to 7 days
118
CAR-T new concern
T-cell malignancies
119
Increased risk pulmonary toxicity with bleomycin
-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
Acid suppressive therapy interactions
-Acalabrutinib capsules
-bosutinib, dasatinib, nilotinib
-erlotinib
-Pazopanib
-Selpercatinib
-sotorasib
-***dacomitinib***
-capecitabine
-gefitinib
-MTX (no PPI)
-Neratinib
-Pexidartinib
-sorafenib
121
VegF monitoring for proteinuria
2+ on urine dipstick or >2 grams of urine protein on 24h urine collection
122
Drugs with interactions with warfarin
-ibrutinib
-capecitabine
-5FU
-gefitinib
-erlotinib
-***aprepitant***
-***TAMOXIFEN***
All increase warfarin effect
123
Management of neutropenia in Hodgkin’s lymphoma
-don’t reduce doses
-don’t use G-CSF (unless BEACOPP or Brentuximab vedotin)
124
Hyperviscosity syndrome
-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
When should you choose palonosetron over other?
Er SubQ granisetron?
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
Weight gain and loss
Gain: lorlatinib, alectinib
Loss: hedgehogs, talquetamab, axitinib, Cabozantinib
127
Gnrh agonist ADRs
-hyperglycemia
-monit ecg and electrolytes
128
Tamoxifen lipids
***hypertriglyceridemia, DECREASES LDL/TC, inc HLD***
129
Hypersensitivity additional points
-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
