Exam 2 Adverse Effects Flashcards
Most anticancer drugs are known to cause myelosuppression except for which drugs?
- VINCRISTINE
- BLEOMYCIN
- corticosteroids
- interferons
- L-asparaginase
- hormones
- methotrexate w/ leucovorin rescue
What are risk factors for myelosuppression?
- Poor marrow reserve (with increasing age)
- Type of chemotherapy
- Prior radiation to the pelvis
- Prior treatment with chemotherapy
- Concurrent treatment with radiation
- Impaired drug elimination
Which drugs do you renally adjust to decrease myelosuppression?
- cisplatin
- carboplatin
- methotrexate
- topotecan
Which drugs do you hepatically adjust to decrease myelosuppression?
- anthracyclines
- vinca alkaloids
- taxanes
- irinotecan
Which drugs are so toxic (myelosuppression) that it takes a long time to recover?
- Busulfan
- Carmustine
define neutropenia
Absolute Neutrophil Count (ANC) < 500/mm^3, or an ANC < 1000/mm^3 with expected to drop less than 500/mm3
What is the number one cause of treatment delays?
neutropenia
define neutropenic fever
neutropenia + fever of 101 degrees F or higher for more than one hour
What are the ways in which you can prevent neutropenia?
- dose reduction
- CSFs
When would you use a CSF to prevent neutropenia?
- if neutropenia (neutropenic fever) incidence is >= 20%
- (use GM-CSF) prevention of neutropenia in patients > 55 receiving induction therapy for AML
G-CSF dosing
5-10 mcg/kg/day SQ until ANC > 10,000/mm3
What are the CSFs?
- Filgrastim: G-CSF
- Pegfilgrastim: G-CSF long acting
- Sargramostim: GM-CSF
What is the administration window for CSFs?
> 24 hours but < 72 hours after start of chemotherapy
What is the benefit of giving G-CSF?
decreases number of febrile days hospital stay and number of antibiotics used
How long does Pegfilgrastim lasts?
14 days
How long do you give Filgrastim for?
until post-nadir ANC recovery to normal or near-normal levels (ANC of 10k)
What is the main adverse effect of CSFs?
- bone pain
- + fever for GM-CSF
When are you most likely to use growth factors? Cure or palliation?
cure
Which agents are commonly associated with thrombocytopenia?
- Topotecan
- Carboplatin
- Gemcitabine
- Bortezomib
When do you treat for thrombocytopenia?
- platelet counts < 10-20,000/mm^3 or < 50,000mm^3 with active bleeding
- fall / injury precautions
When should you give blood / platelet infusion in thrombocytopenia?
when platelet drops below 10k
What can you do to prevent thrombocytopenia?
- Interleukin-11 (oprelvekin)
- Dose reduction
Interleukin-11 (oprelvekin) MOA
stimulates platelet production through the stimulation of megakaryocytopoiesis and thrombopoiesis
Interleukin-11 (oprelvekin) dose
50 µg/kg SC once daily 6-24 hours after chemo until post-nadir platelet count is 100k cells/µL or for 21 days
Which agents are commonly associated with anemia?
- cisplatin
- carboplatin
- but can occur with any marrow toxic agent
Treatment / prevention of anemia
Transfusion of packed red blood cells (PRBCs) for hemoglobin < 8gm/dL or higher if severely symptomatic
What does EPO do?
speeds up process of stem cell differentiating into red blood cell
Erythopoietin (Procrit®) dosing
- 100-150 units/kg SQ three times a week or 40,000 units once a week
- can only increase dose once
When should you give Erythopoietin (Procrit®)?
give to high risk patients with hemoglobins <10gm/dL prior to chemotherapy
Darbepoetin alfa dosing
- know 500mcg every 3 weeks
- 1.5 mcg/kg/week to 6 mcg/kg every 3 weeks
Which drugs are most commonly associated with mucositis?
- 5-Fluorouracil (esp w/ bolus)
- Methotrexate
- Doxorubicin
- Taxanes
risk factors for mucositis
- Poor oral hygiene/dentures
- Leukemia / lymphoma
- Young age
- Radiation therapy
- Poor nutritional status
- High dose therapy
prevention of mucositis
- Oral hygiene
- Pretreatment dental evaluation
- Oral cryotherapy (ice chips)
- Leucovorin rescue (for methotrexate)
- Colony-stimulating factors? (theoretical benefit)
treatment of mucositis
- analgesics
- antifungal agents
- antiviral agents: acyclovir
- antibiotics: vancomycin
- growth factor: Palifermin
risk factors for diarrhea
- elderly
- female
Which agents are most commonly associated with diarrhea?
- 5-FU
- Interleukin-2
- Irinotecan
- Erlotinib (KNOW THIS)
- EGFR agents
- oral VEGF inhibitors
- ipilimumab (50% chance)
Which agent can cause both early and late diarrhea?
Irinotecan
How do you treat diarrhea caused by irinotecan?
- Treat early diarrhea with anticholinergics
- Late diarrhea treated with loperamide (4mg stat and then 2mg Q2 hours until diarrhea stops)
treatment of diarrhea (no prevention)
- Loperamide
- Octreotide
- steroids 1-2mg/kg methylprednison
- hydration
- electrolyte supplementation
- bowel rest
- nutritional support
Grade 2 diarrhea treatment
oral diphenoxylate hydrochloride and atropine sulfate four times per day and budesonide 9 mg once per day
Grade 3 or 4 diarrhea treatment
- 1–2 mg/kg/day methylprednisolone
- no improvement or relapse: single dose of infliximab 5 mg/kg
Which agents are most likely associated with constipation?
- Vinca alkaloids: Vincristine, vinblastine, vinorelbine
- Patients on pain medications
prevention of constipation
- Stool softeners
- stimulant / hyperosmotic laxatives
treatment of constipation
- Increased laxatives
- Methylnaltrexone ( esp. if opioid induced) (1 time dose usually effective)
- Disimpaction
- enemas
- NG tube
Which agents are most likely to cause renal toxicity?
- Cisplatin - Tubular necrosis and electrolyte wasting
- High dose methotrexate -Precipitates in renal tubules
- Ifosfamide, high dose cyclophosphamide
Which patients are as risk for developing renal toxicity?
- Pre-existing renal dysfunction
- Concurrent use of other nephrotoxic drugs (e.g. cisplatin, aminoglycosides, amphotericin, NSAIDs)
- High dose therapy or increased cumulative dose
prevention of nephrotoxicity with cisplatin
- hydrate with 1L of NS + 20mEq K + 8 mEq of Mg over 1-2 hours to obtain a urine flow rate of 100mL/hour
- then give dieuretics (furosemide)
- Change to less nephrotoxic analog (carboplatin)
- Amifostine (Ethyol)
treatment of nephrotoxicity with cisplatin
- Hydration, replacement of electrolytes
- Discontinuation other nephrotoxins
- Dialysis
Amifostine (Ethyol) MOA
- only protects healthy cells
- gets converted into a compound that goes into cell to protect it
- give BEFORE cisplatin
prevention of nephrotoxicity with methotrexate
- Alkalinization of urine to pH >= 7
- Sodium bicarbonate beginning 12 hours prior and continuing 24 hours after
- Dose adjustment for renal insufficiency
Which agents are most commonly associated with bladder toxicity?
- Cyclophosphamide
- Ifosfamide
MOA of bladder toxicity
- Cyclophosphamide gets broken down into active components phosphoramide mustard and acrolein
- acrolein is the cytotoxic agent to the bladder
prevention of bladder toxicity
- Vigorous hydration
- Administer with mesna (binds to acrolein)
treatment of bladder toxicity
- Increased hydration
- Mesna
- Bladder irrigation
- Hyperbaric oxygen, prostaglandin E2, formalin
- Cystectomy for refractory cases
mesna dosing IV
20% of ifosfamide dose immediately before and then 20% of dose 4 and 8 hours after IV boluses of ifosfamide
mesna dosing PO
20% of ifosfamide dose immediately before and then 40% of dose 2 and 6 hours after IV boluses of ifosfamide
Which agents are most likely to cause cardiac toxicity?
- Anthracyclines (Doxorubicin, Daunorubicin, Idarubicin)
- Mitoxantrone
- Her2-targeted agents
- VEGF and BCR-ABL inhibitors
What are the types of cardiotoxicity that Anthracyclines can cause?
- Acute: Arrhythmias
- Subacute: Toxic myocarditis, pericarditis
- Chronic: CHF Late:
- Ventricular dysfunction
Anthracyclines max doses
- Doxorubicin doses > 450-550mg/m^2
- Daunorubicin doses > 450-550mg/m^2
- Idarubicin doses > 150mg/m^2
- Epirubicin doses > 900mg/m^2
Risk factors for Anthracycline-related cardiotoxicity
- Bolus infusions (less prolonged infusion)
- Older age
- Pre-existing cardiac disease
- Previous mediastinal irradiation
prevention of Anthracycline-related cardiotoxicity
- All patients should have a baseline MUGA done to evaluate potential cardiotoxicity (ejection fraction should be >50%)
- give as continuous infusion instead of bolus
- limit total cumulative dose
- dexrazoxane
dexrazoxane MOA
Metal chelator that strips doxorubicin from iron complexes, & prevents generation of free oxygen radicals
Which drugs cause QT prolongation?
BCR-Abl drugs: imatinib, dasatinib, nilotibib
Which drugs cause hypertension?
VEGF-drugs: sunitinib, sorafenib, bevacizumab
Treatment with tyrosine kinase should not be started in which patients?
pts who have excessive corrected QT prolongation > 500ms
Which drugs are most commonly associated with pulmonary toxicity?
- Bleomycin (4% incidence)
- All trans-retinoic acid - “Retinoic acid syndrome”
- EGFR inhibitors
- mTOR inhibitors
Prevention of bleomycin related pulmonary toxicity
Limit total cumulative dose to < 400 units total of bleomycin
Which agents are most commonly associated with neurotoxicity?
- Vinca alkaloids (especially vincristine)
- Cisplatin
- Oxaliplatin
- Bortezomib
- Taxanes and Epothilones
- Ifosfamide
- Brentuximab vedotin
- High dose cytarabine
prevention of neurotoxicity
- No known method – Amifostine or gabapentin?
- Avoid cold temperatures for oxaliplatin (exacerbated)
- Use in appropriate patients
treatment of neurotoxicity
- Supportive care: Analgesics for pain
- Amifostine?
Which drugs are most commonly associated with alopecia?
Anthracyclines and Taxol®, many others as well
prevention of alopecia
ice caps
treatment of alopecia
wigs, scarves, hat
Which drugs are most commonly associated with photosensitivity?
- 5-FU, MTX
- all-trans retinoic acid
prevention of photosensitivity
Wear sunscreen SPF > 30, or preferably sun block
treatment of photosensitivity
Supportive-Topical lotions
Which drugs are most commonly associated with acne like rash?
EGFR
treatment for mild rash
topical steroid or cream
AND/OR clindamycin gel
treatment for moderate rash
topical steroid higher potency or clindamycin gel
AND oral doxy
treatment for severe rash
topical steroid higher potency or clindamycin gel
AND oral doxy
AND steroid dose pack
Which agents are most likely associated with hand-foot syndrome?
- capecitabine
- infusion 5FU
- oral tyrosine kinase inhibitors (sunitinib, sorafenib)
treatment for hand-foot syndrome
- Dose reduction
- Avoid tight-fitting shoes; repetitive rubbing or prolonged heat to hands and feet
- keep areas moist
Which agents are vesicants?
- Anthracyclines
- vinca alkaloids
- nitrogen mustards (mechlorethamine)
- mitomycin C
- dactinomycin
prevention of vesicants
- use central venous catheters
- have experienced nurse administer drug
treatment of vesicants
- stop infusion
- withdraw fluid
- ice packs for all drugs except vinca (use heat for vinca)
antidote for nitrogen mustard
sodium thiosulfate
antidote for vinca
hyaluronidase
antidote for Anthracyclines
DMSO or dexrazoxane
Totect (Dexrazoxane) dosing
- Day 1: 1000 mg/m2
- Day 2: 1000 mg/m2
- Day 3: 500 mg/m2
- do not exceed 2000mg at any one time
Which agents are most likely associated with hypersensitivity reactions?
- L-asparaginase
- Paclitaxel
- Bleomycin (rare)
- Cisplatin
- Anthracyclines (hives as local infusion site)
prevention of hypersensitivity reactionso
- L-asparaginase: Give 2 unit test dose, avoid IV administration of the drug
- Paclitaxel: Premedicate with steroids, H1- and H2-blockers
- Bleomycin: 1 mg (1 unit) test dose
treatment of hypersensitivity reactions
- Corticosteroids
- epinephrine
- antihistamines (H1 and H2 blockers)
