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