Toxicities Flashcards
Diarrhea
-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
Thrombocytopenia
-Carboplatin
-Gemcitabine
-mitomycin
-Procarbazine
-Vinorelbine
Hep B reactivation
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+
Hypersensitivity rxns
-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
Extravasation
-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
Electrolyte disturbances
-EGFR inhibitors- hypomag
-platinums- hypo: mag, ca, na, phos, k
-arsenic trioxide: hypo: k, mg, ca, also causes QTc prolongation
-FGFR inhibitors: hyperphos
Nephrotoxicity
-platinums
-cisplatin- pre and post hydration
-Carboplatin
-alkylating agents: cyclophosphamide, ifosfamide, bendamustine
-VEGF inhibitors: bevacizumab-proteinuria- need UA
-immune checkpoint inhibitors: immune mediated nephritis
Hemorrhagic cystitis
-HD cyclophosphamide
-ifosphamide
*give Mesna to bind acrolein
-other tricks: IVF, aminocaproic acid, Alum
Pulmonary toxicity
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
Dermatological toxicity
-immune checkpoint inhibitors
-EGFR inhibitors: cetuximab and panitumumab are notorious but this means better tx response
Ocular toxicity
-immune checkpoint inhibitors
-belantumab madofotin-off market
-tisotumab vedotin
-mivertuximab soravtansine
Neuropathy
-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
Cold sensitivity
Oxaliplatin
Neurotoxicity
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
Immune mediated ADRs
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
Cardiotoxicity
-Anthracyclines: permanent
-HER-2 inhibitors: can be reversible
-checkpoint inhibitors: myocarditis
-5FU/capecitabine: vasospasms
-VEGF inhibitors: hemorrhage, VTE, HTN
-TKIs: QTC, arrhythmias
HTN
VEGF inhibitors, copanlisib, proteosome inhibitors, prostate drugs, RAF inhibitors, MEK inhibitors, ALK inhibitors
ESAs, NSAIDS, corticosteroids, trapiluspatercept
High emetogenic risk (<90%) IV
-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
Moderate to high emetogenic risk (PO)
-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
Emetogenic risk by radiation site
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
Known risk of TdP
Vandetanib, Oxaliplatin, mobocertinib, arsenic trioxide
VEGFR
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)
BRAF
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
RAF
On target: hand foot syndrome, rash
MEK
On target: none..?
Other: cardiomyopathy, fever, eye disorders
CDK 4/6
On target: myelosuppression, alopecia, nausea, mucositis
Other: pulmonary embolism, interstitial lung dx
EGFR
On target: rash, diarrhea, paronychia
Other: interstitial lung dx
USE SUNSCREEN
ALK and/ or ROS1
On target: bradycardia, visual disturbances
Other: interstitial lung dx, low-T (crizotinib), CNS toxicity (lorlatinib), increased CPK (Brigatinib, alectinib)
PARP inhibitors
-myelosuppression (especially anemia)
-less with Niraparib
-monitor CBC
-secondary leukemia/MDS
-Fatigue, GI
FGFR
On target: hyperphosphatemia
Other: eye disorders
HER-2
On target: LVEF dysfunction, diarrhea
RET
On target: hypothyroidism
Other: hypersensitivity (selpercatinib), QTc (Selpercatinib)
VEGF ADRs: HTN, impaired would healing, hepatotoxicity
MET
On target: Hepatotoxicity
Peripheral edema, hepatotoxicity, ILD
Capmatinib, tepotinib
NTRK
On target: CNS toxicity (including eye disorders), fractures
Other: edema
MTOR
On target: metabolic issues, impaired wound healing, infection, mucositis (NOT hand/foot syndrome)
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
FLT3
On target: myelosuppression
Differentiation syndrome
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
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)
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
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
How to handle trastuzumab cardio toxicity
Hold, and rechallenge if EF recovers
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
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
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
Which cdk 4/6 inhibitor increases QTc?
Ribociclib
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
How often to get echo for traztuzumab?
-Q3 months during and upon completion
-Q6 months x2 years after completion
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,
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
Common ADR of “armed antibodies”
Thrombocytopenia
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
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
All TKIs
Diarrhea, rash, fatigue, transaminitis/hepatotoxicity, embyo-fetal toxicity
Possible slightly increased risk of developing other cancers
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
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)
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
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
General grading of toxicity
Grade 1: annoying
Grade 2: affects ADLs
Grade 3: requires hospitalization
Grade 4: life threatening
Grade 5: death
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
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)
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
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)
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
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.
AI myalgias
-starts at ~6 weeks and can worsen over a year
-tx with duloxetine, acupuncture, Exercise
-change to another AI
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
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
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
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
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)
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
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
What causes Pediatrics: growth hormone deficiency or metabolic syndrome/ obesity risk factors?
Head/brain/TBI
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
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
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
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
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
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
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
SVC syndrome
Causes: lung, lymphoma
Other: head/neck, breast, thymoma, germ cell
Treatment:
Surgery, chemo-RT (lymphoma, SCLC), stent, RT
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
Capecitabine vs 5FU
Capecitabine has less stomatitis, alopecia, and neutropenia but MORE hand/foot syndrome and hyperbilirubinemia
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!!!
Calcium levels to tx hypercalcemia
-<12 and no symptoms: don’t tx
-<12-14: tx esp if symptoms
->14 tx regardless of symptoms
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
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)
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
Coasting
Ongoing neuropathy after stopping treatment
CAPOX v FOLFOX
CAPOX is harder to tolerate
Symptoms indicative of true hypersensitivity rxn as opposed to infusion rxn
Angioedema, urticaria, nasal congestion, dysphonia, wheezing
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
Oxaliplatin vs cisplatin
Generally Oxaliplatin is better tolerated, but it does have more neuropathy
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
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
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
IRAE hypophysitis
Pituitary dysfunction- Loss of cortisol, fails cortisol test
Give steroid
This is usually permanent!!
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
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
Targeted therapy with heart transplant
-HER-2 therapy ok since new healthy heart
-No ICIs d/t risk for organ rejection
Prevention of hearing loss with cisplatin
-sodium thiosulfate: only if NON-metastatic hepatoblastoma
-don’t prolong infusion and don’t use Amifostine
Why is albumin given with ifosphamide
Neurotoxicity prevention
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
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
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
ICI toxicity management via dose interruptions/dose adjustment
-dose interruption but don’t decrease dose after restarting
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
Risk factors for CINV
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+
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
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
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
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
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
Intravesical chemo
-Chemical cystitis (azo and anticholinergics)
-eczema desquamization- avoid urine contact/wash hands
-use condoms x48 hours
Dexamethasone hiccups
Switch to methylprednisolone
Dex 8-12 mg —> MP 40-64 mg
Taxane acute pain syndrome
Myalgias/arthralgias
Starts 24-48he after and lasts up to 7 days
CAR-T new concern
T-cell malignancies
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
Acid suppressive therapy interactions
-Acalabrutinib capsules
-bosutinib, dasatinib, nilotinib
-erlotinib
-Pazopanib
-Selpercatinib
-sotorasib
-dacomitinib
-capecitabine
-gefitinib
-MTX (no PPI)
-Neratinib
-Pexidartinib
-sorafenib
VegF monitoring for proteinuria
2+ on urine dipstick or >2 grams of urine protein on 24h urine collection
Drugs with interactions with warfarin
-ibrutinib
-capecitabine
-5FU
-gefitinib
-erlotinib
-aprepitant
-TAMOXIFEN
All increase warfarin effect
Management of neutropenia in Hodgkin’s lymphoma
-don’t reduce doses
-don’t use G-CSF (unless BEACOPP or Brentuximab vedotin)
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
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
Weight gain and loss
Gain: lorlatinib, alectinib
Loss: hedgehogs, talquetamab, axitinib, Cabozantinib
Gnrh agonist ADRs
-hyperglycemia
-monit ecg and electrolytes
Tamoxifen lipids
hypertriglyceridemia, DECREASES LDL/TC, inc HLD
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
