Chapter 61 - Oncology 1 Flashcards
1
Q
Carcinoma
A
Cancer that starts in skin or in the tissues that line or cover internal organs.
2
Q
Leukemia
A
Cancer of the leukocytes (WBCs); leukemia is referred to as blood cancer.
3
Q
Lymphoma
A
Cancer of the lymphatic system.
4
Q
Multiple Myeloma
A
A type of bone marrow cancer.
5
Q
Sarcoma
A
Cancer in connective tissue (tissue that connects, supports, binds or separates other tissues), including fat, muscle, blood vessels and bone. Osteosarcoma is a type of bone cancer.
6
Q
Skin Cancers:
Basal Cell & Squamous Cell Carcinomas and Melanoma
A
Basal Cell and Squamous Cell Carcinoma: common, unlikely to metastasize, rather simple to remove surgically or with topical treatment.
Melanoma: skin cancer that forms in the melanocytes [the skin cells that produce the pigment (melanin) that colors skin]. Least prevalent type of skin cancer (2%), but most deadly.
7
Q
Breast Cancer Screening
A
40-44 years –> Annual mammograms are optional
45 - 54 years –> Begin yearly mammograms
> =55 years –> Mammograms every 2 years or continue yearly
8
Q
Cervical Cancer Screening
A
21-29 years –> Pap smear every 3 years
30-65 years –> Papsmear+ HPV (Human papillomavirus) DNA test every 5 years
9
Q
Colon Cancer Screening
A
> = 45 years (M/F)
Stool-based tests (if positive, follow with a colonoscopy)
■ Highly sensitive fecal immunochemical test (FIT) every year Highly sensitive guaiac-based fecal occult blood test (gFOBT) every year
■ Multi-targeted stool DNA test (MT-sDNA) every 3 years
Visual exams of the colon and rectum:
■ Colonoscopyevery10years
■ CT colonography (virtual colonoscopy) every 5 years
■ Flexible sigmoidoscopy (FSIG)every 5 years
10
Q
Lung Cancer Screening
A
55 - 74 years
Annual CT scanof chest if all of the following:
■ In good health
■ Have at least a 30 pack-year smoking history
■ Still smoking or quit smoking within the past 15 years
11
Q
Prostate Cancer Screening
A
> = 50
If a patient chooses to be tested, it involves:
■ Prostate specific antigen (PSA) test (blood test)
■ +/- a digital rectal exam (DRE)
12
Q
amifostine (ethyol) is given …
A
with cisplatin to prophylactically reduce risk of nephrotoxicity
13
Q
dexrazoxane is given …
A
with doxorubicin to prophylactically reduce risk of cardiomyopathy
14
Q
Chemotherapy drugs is CI in
A
Pregnancy and breastfeeding
use a form of contraception
Male and female patients must avoid conceiving during treatment.
15
Q
Bleomycin Max dose
A
Lifetime cumulative dose: 400 units
Reason: Pulmonary fibrosis
16
Q
Doxorubicin Max dose
A
Lifetime cumulative dose: 450 - 550 units/m2 (BSA)
Reason: Cariotoxicity
17
Q
Cisplatin Max dose
A
Dose per cycle not to exceed 100 mg/m’
Reason: Nephrotoxicity
18
Q
Vincristine Max dose
A
Single dose “capped” at 2 mg
Reason: Neuropathy
19
Q
drugs that cause: Myelosuppression
A
Almost all classic chemotherapy drugs, except:
Asearaginase, bleomycin, vincristine, most monoclonal antibodies (MAbs) and many tyrosine kinase inhibitors (TKls)
Monitoring: Complete blood count (CBC) with differential, temperature, bleeding, fatigue, shortness of breath
Management:
Neutropenia: colony-stimulating factors (CSFs)
Anemia: RBC transfusions, and (in palliation only) erythropoiesis-stimulating agents (ESAs)
Thrombocytopenia: platelet transfusions (when very low, especially if bleeding)
20
Q
Drugs that cause: Nausea & Vomiting
A
Cisplatin, cyclophosphamide, ifosfamide, doxorubicin, epirubicin
Monitoring: Patient symptoms of nausea and vomiting and dehydration
Management:
Neurokinin-1 receptor antagonist (NK1-RA),
Serotonin-3 receetor antagonist (5HT3-RA),
dexamethasone, metoclopramide, prochlorperazine
IV/PO fluid hydration
21
Q
Drugs that cause: Mucositis
A
Fluorouracil, methotrexate, capecitabine, irinotecan and many TKls (afatinib, ponatinib, sorafenib, sunitinib)
Monitoring: S/sx of superinfection of oral ulcers with herpes simplex virus or thrush (Candida species)
Management:
Symetomatic treatment: mucosal coating agents,
topical local anesthetics (e.g., lidocaine viscous), antifungals, antivirals
22
Q
Drugs that cause: Diarrhea
A
Fluorouracil, methotrexate, capecitabine, lrinotecan and many TKls
Monitoring: Frequency of bowel movements, hydration status, potassium and other electrolytes
Management:
IV/PO fluid hydration, antimotility medications (e.g.,loperamide)
lrinotecan: atropine for early-onset diarrhea
23
Q
Drugs that cause: Diarrhea
A
Vincristine, pomalidomide, thalidomide
Monitoring:
Frequency of bowel movements
Management:
Stimulant laxatives, polyethylene glycol (PEG3350, Miralax)
24
Q
Treatment that causes: Xerostomia
A
Caused by radiation therapy to the head or neck regions
Monitoring:
Dry mouth
Management:
Artificial saliva substitutes, pilocarpine, amifostine
25
Drugs that cause: Cardiotoxicity
- CARDIOMYOPATHY
Anthracyclines, HER2 inhibitors (ado- trastuzumab, trastuzumab, pertuzumab, lapatinib), fluorouracil
Monitoring:
Left ventricular ejection fraction (LVEF),lifetime cumulative dose of anthracycline
Management:
Do not exceed recommended lifetime cumulative dose of 450-550 mg/m 2 for doxorubicin; give dexrazoxane prophylactically in select patients receiving doxorubicin
- QT PROLONGATION
Arsenic trioxide, many TKls (dasatinib, nilotinib, vemurafenib, dabrafenib, trametinib, crizotinib, ceritinib, erlotinib, gefitinib, lapatinib, sorafenib, sunitinib) and leuprolide
Monitoring: ECG, K, Mg, Ca
Management:
Keep K, Mg, Ca within normal limits, consider holding therapy if QTc > 500 msec
26
Drugs that cause: Pulmonary Toxicity (pulmonary fibrosis or pneumonitis)
- Pulmonary fibrosis
Bleomycin, busulfan, carmustine, lomustine
- Pneumonitis
Methotrexate
immune therapy MAbs targeting CTLA- 4 or PD-1: atezolizumab, durvalumab,
ipilimumab, nivolumab, pembrolizumab
Monitoring:
- Oxygen saturation, ABGs, symptoms (shortness of breath, dyspnea on exertion)
- Maximum lifetime dose of bleomycin 400 units
Management:
- Symptomatic management
- Stop therapy
- Steroids (if an autoimmune mechanism is suspected) for immunotherapy agents
27
Drugs that cause: Hepatotoxicity
Antiandrogens (bicalutamide, flutamide, nilutamide), folate antimetabolites {methotrexate, pemetrexed, pralatrexate), pyrimidine analogantimetabolites {cytarabine, gemcitabine), many tyrosine kinase inhibitors, ipilimumab, pembrolizumab, nivolumab, atezolizumab, durvalumab
Monitoring:
LFTs, jaundice, ascites
Management:
- Symptomatic management
- Consider stopping therapy
- Steroids (if an autoimmune mechanism is suspected) for immunotherapy agents (e.g., for CTLA·4 or PD· 1
- immune therapy MAbs - atezolizumab, durvalumab, ipilimumab, nivolumab and pembrolizumab)
28
Drugs that cause: Nephrotoxicity
- Cisplatin
- Methotrexate (high doses), pemetrexed, pralatrexate, carfilzomib, bevacizumab, nivolumab, pembrolizumab, ipilimumab, atezolizumab, durvalumab
Monitoring
BUN, SCr, urinalysis, urine output, creatinine clearance
Management
Amifostine (Ethyol) can be given prophylactically with cisplatin to reduce the risk of nephrotoxicity
Ensure adequate hydration
Do not exceed maximum dose of 100 mg/m'/cycle for cisplatin
29
Drugs that cause: Hemorrhagic cystitis
lfosfamide (all doses),cyclophosphamide (higher doses, e.g., > 1 gram/m')
Monitoring:
Urinalysis for blood, symptoms of dysuria
Mesna (Mesnex) is always given prophylactically with ifosfamide (and sometimes with cyclophosphamide) to reduce the risk of hemorrhagic cystitis
Always ensure adequate hydration
30
Drugs that cause: Neuropathy
- Peripheral Neuropathy
Vinca alkaloids {vincristine, vinblastine, vinorelbine)
Platinums (cisplatin, oxaliplatin)
Taxanes{paclitaxel, docetaxel, cabazitaxel)
Proteasome inhibitors (bortezomib, carfilzomib), thalidomide, ado·trastuzumab, cytarabine (high doses), brentuximab
Monitoring:
S/sx of paresthesias (pain, tingling, numbness)
- Autonomic Neuropathy
Vinca alkaloids
Monitoring:
- Constipation
- Symptomatic treatment with drugs for neuropathic pain
- Vincristine
Many recommend limiting the dose of vincristine to 2 mg per week (regardless of BSA calculated dose)
-Oxaliplatin
Causes an acute cold-mediated sensory neuropathy; instruct patients to avoid cold temperatures and avoid drinking cold beverages
-Bortezomib
SC administration is associated with less peripheral neuropathy than IV administration
31
Drugs that cause: Thromboembolic risk (clotting)
Aromatase inhibitors (e.g.,anastrozole, letrozole), SERMs (e.g.,tamoxifen, raloxifene), immunomodulators (thalidomide, lenalidomide, pomalidomide)
Monitoring:
S/sx of DVT/PE, stroke, Ml
Management:
Consider thromboprophylaxis risk factors based on the patient's risk factors
32
CHEMOTHERAPY ADJUNCTIVE TREATMENT- cisplatin
Amifostine (Ethyol) and hydration
Prophylaxis to prevent nephrotoxicity
33
CHEMOTHERAPY ADJUNCTIVE TREATMENT - Doxorubicin
Dexrazoxane (Zinecard,Totect)
Prophylaxis to prevent cardiomyopathy
34
CHEMOTHERAPY ADJUNCTIVE TREATMENT - Fluorouracil
Leucovorin or levoleucovorin (Fusilev)
Given with fluorouracil to enhance efficacy (as a cofactor)
35
CHEMOTHERAPY ADJUNCTIVE TREATMENT - Fluorouracil or capecitabine
Uridine triacetate (Vistogard)
Antidote: use within 96 hours for an overdose or to treat severe, life-threatening or early-onset toxicity
36
CHEMOTHERAPY ADJUNCTIVE TREATMENT - lfosfamide
Mesna /Mesnex) Hydration
Prophylaxis to prevent hemorrhagic cystitis
37
CHEMOTHERAPY ADJUNCTIVE TREATMENT- Irinotecan
Atropine
Prevent or treat acute diarrhea
Loperamide
Treat delayed diarrhea
38
CHEMOTHERAPY ADJUNCTIVE TREATMENT - Methotrexate
Leucovorin or levoleucovorin (Fusilev)
Given prophylactically after methotrexate to dec myelosuppression and mucositis in high-dose therapy
Glucarpidase (Voraxaze)
An antidote to dec excessive methotrexate levels due to acute renal failure
39
capecitabine is a ...
prodrug of 5 fu developed to mimic the continuous infusion of 5fu while avoiding complications of iv administration
40
what is Myelosuppression
Myelosuppression (dec in bone marrow activity, resulting in fewer (RBCs, WBCs and platelets) is a complication of most chemotherapy regimens
41
Epoetin alfa
Epogen,Procrit
42
Darbepoetin alfa
Aranesp
43
Filgrastim
Neupogen
Nivestym, Zarxio
44
Pegfilgrastim
Neulasta
only used as prophylactic
45
WBC nadir
The lowest point that WBCs and platelets reach is called the nadir, which occurs {with most drugs} about 7 - 14 days after chemotherapy.
46
RBC nadir
The RBC nadir is much later, generally after several months of treatment, due to the long life span of RBCs (-120 days).
47
trilaciclib (Cosela)
In early 2021, the kinase-inhibitor trilaciclib (Cosela) was approved to decrease myelosuppression from extensive-stage small cell lung cancer treatment.
It is given as an IV infusion within four hours prior to the start of platinum/etoposide or topotecan- containing chemotherapy regimens.
48
Neutropenia
Neutropenia, a type of leukopenia, is a low neutrophil count that is assessed by calculating an absolute neutrophil count {ANC).
The more significant the neutropenia (i.e., the lower the ANC), the higher the risk of infection.
49
ANC calculation
ANC cells/mm3 = WBC x (% segs + % bands)/100
50
Neutropenia anc
< 1,000 cells/mm'
51
Severe Neutropenia anc
< 500 cells/mm'
52
Profound Neutropenia anc
< 100 cells/mm3
53
Growth Colony Stimulating Factors
(G-CSFs,or simply CSFsor "myeloid growth factors") stimulate the production of WBCs in the bone marrow.
Myeloid refers to the granulocyte precursor cell, which differentiates into neutrophils, eosinophils and basophils.
CSFs are given prophylactically after chemotherapy to shorten the time that a patient is at risk for infection due to neutropenia and reduce mortality from infections.
They are used to prevent {or reduce) neutropenia, not for acute treatment.
54
do not give filgrastim is ANC is
> 10, 000 cells/mm3
55
filgrastim dosing
5 mcg/kg/day given IV/SC daily (round to the nearest 300 mcg or 480 mcg vial size); treat through post-nadir recovery (until ANC >2,000-3,000 cells/mm3)
10 mcg/kg/day used for bone marrow transplant
56
Pegfilgrastim dosing
1 prefilled syringe (6 mg) SC once
per chemo cycle (pegfilgrastim is pegylated, extending the half-life)
57
Sargramostim dosing
250 mcg/m/day given IV/SC daily; treat through post-nadir recovery
58
Sargramostim brand
Leukine
Limited to use in stem cell transplantation
59
tbo-filgrastim brand
Granix
biosimilar to filgrastim
60
Biosimilars to peg-filgrastim
- apgf (Nyvepria)
- bmez (Ziextenzo)
- cbqv (Udenyca)
- jmdb (Fulphila)
61
se of Filgrastim/ pegfilgrastim/ tbo-filgrastim:
bone pain, fever, glomerulonephritis, generalized rash, injection site reaction
62
se of Sargramostim
fever, bone pain, arthralgias, myalgias, rash, dyspnea, peripheral
edema, pericardia! effusion, HTN, chest pain
63
monitoring with csf
CBC with differential, pulmonary function, weight, vital signs
64
1) how should you store csf
2) when should you administer?
3) what should patients report as SE
4) when should pegfilgrastim be given
1) Store in refrigerator; protect vials from light
2) Administer first dose no sooner than 24 hours after chemo; can be up to
96 hours after chemo
3) Patients should report any signs of enlarged spleen (pain in left upper abdomen ~ or respiratory distress syndrome)
4) Pegfilgrastim: must document when given; should have at least 12 days to the next chemo cycle
65
1) when do you start emperic abx?
Infection can be difficult to diagnose; fever may be the only sign of infection in a neutropenic patient (i.e., the increase in WBC count will not be present).
Empiric antibiotics are started immediately if a fever occurs.
66
Neutropenia Diagnosis Requirements
fever:
Oral temperature > 38.3°C (101°F) x 1 reading, or
Oral temperature > 38.0°C (100.4°F) sustained for > 1 hour
Neutropenia:
Absolute neutrophil count (ANC<) 500 cells/mm3, or
ANC that is expected to dec to < 500 cells/mm3 during the next 48 hours
67
low risk of infection
Expected ANC< 500 cells/mm3 for <= 7 days
No comorbidities
Initial empiric abx: Oral anti-pseudomonal antibiotics
- Oral anti-pseudomonal antibiotics
Ciprofloxacin or levofloxacin PLUS
- Amoxicillin/clavulanate (G+) or clindamycin (G+ & anaerobic) (if allergic to penicillin)
68
high risk of infection
Expected ANC <= 100 cells/mm' for > 7 days
&/or
Presence of comorbidities
&/or
Evidence of renal or hepatic impairment (CrCl< 30 ml/minor LFTs > 5x ULN)
Initial empiric abx: Intravenous anti-pseudomonal beta-lactams
- Cefepime or
- Ceftazidime or
- Meropenem or
- lmipenem/cilastatin or
- Piperacillin/tazobacta
69
What levels are used to assess anemia.
What are the normal levels
Hemoglobin
Normal Hgb levels are 12 - 16 g/dL for females and 13.5 - 18 g/dL for males {hematocrit is 36 - 46% females; 38 - 50% males).
70
What are the 3 ways for resolution of anemia (ttmt)
- without treatment
- RBC transfusion
- erythropoiesis-stimulating agent (ESA)
71
ESA types
ESA risks
When should you use ESA
ESAs include:
- epoetin alfa (Epoqen, Procrit),
- epoetin alfa-epbx (Retacrit) and
- the longer-acting darbepoetin alfa (Aranesp).
ESAs can shorten survival and inc tumor progression (i.e., they can contribute to cancer growth).
Therefore, ESAs are for palliation and are not recommended to be used in patients receiving chemotherapy with curative intent.
72
What criteria should be met to minimize the risks of ESAs in patients with chemotherapy-induced anemia
■ Use ESAs only in patients with non-myeloid malignancies where anemia is due to the effect of the chemotherapy.
■ Upon initiation of ESA therapy, there must be a minimum of two additional months of planned chemotherapy.
■ Initiate ESAs only when the Hgb is < 10g/dL.
■ Use the lowest dose needed to avoid RBCtransfusions.
73
..., ... and ... must be assessed since ESAs will not work well to correct the anemia if iron levels are inadequate.
Levels of ... and ... may need to be evaluated, especially if there is a poor response to the ESA
Serum ferritin, transferrin saturation (TSAT) and total iron-binding capacity (TIBC) must be assessed since ESAs will not work well to correct the anemia if iron levels are inadequate.
Levels of folate and vitamin Bl2 may need to be evaluated, especially if there is a poor response to the ESA
74
The normal range for platelets is ...
150,000 - 450,000/mm3
75
The risk for spontaneous bleeding is increased when the platelet count is < ...
10,000 cells/mm3
76
Platelet transfusions are generally indicated when:
- the count falls below 10,000 cells/mm3
- or< 30,000 cells/mm 3 if active bleeding is present
77
What should you avoid in patients who are thrombocytopenic.
Intramuscular injections and medications that affect platelet functioning, such as NSAIDs
78
Patient factors that increase the risk of nausea and vomiting include:
- female gender,
- age < 5O years,
- anxiety, depression,
- dehydration,
- history of motion sickness
- history of nausea and vomiting with prior regimens
79
Acute CINV
1) Onset
2) Risk factors
3) Major neurotransmitters
4) Drug therapy
1) Within 24 hours after chemo
2) Female gender, age < 5O years, anxiety, depression, dehydration, history of motion sickness and history of nausea and vomiting with prior regimens.
3) Serotonin and Substance P
4) 5HT3 receptor antagonists (5HT3-RA). NK1 receptor antagonists (NK1-RA), dexamethasone and olanzapine
80
Delayed CINV
1) Onset
2) Risk factors
3) Major neurotransmitters
4) Drug therapy
1) > 24 hours after chemo
2) Anthracyclines, platinum analogs, cyclophosphamide, ifosfamide, any chemo regimens with a high risk for causing acute Cl NV
3) Substance P and Dopamine
4) NK1-RA, corticosteroids, palonosetron or granisetron ER SC (only 5HT3·RAs with a labeled indication for delayed emesis) and olanzapine
81
Anticipatory CINV
1) Onset
2) Risk factors
3) Major neurotransmitters
4) Drug therapy
1) Before chemo
2) History of CINV with previous chemo regimen
3) GammaAminobutyric Acid (GABA)
4) Benzodiazepines; start the evening prior to chemotherapy to alleviate anxiety and N/V
82
What 5HT3-RA are FDA approved for delayed CINV
- Palonosetron
- Sustol (granisetron) SC
83
5-HT3 RA
- Ondansetron
- Granisetron
- Dolasetron
- Palonosetron
84
NK1 RA
- Aprepitant PO
- Fosaprepitant IV
- Rolapitant
85
1) combination: 5ht3ra & NK1RA
2) Others
3) Dexamethasone
1) Akynzeo
- Netupitant/palonosetron PO
- Fosnetupitant/palonosetron IV
2) Olanzapine
3) Dexamethasone
86
High emetic risk chemotherapy regimen
3 or 4 drugs:
■ NKl-RA + 5HT3-RA + Olanzapine + Dexamethasone (preferred)
- Olanzapine +
- netupitant or fosnetupitant/ palonosetron (Akynzeo) +
- dexamethasone
■ Palonosetron + Olanzapine + Dexamethasone
■ NKl-RA + 5HT3-RA + Dexamethasone
- Netupitant or fosnetupitant/ palonosetron (Akynzeo) + dexamethasone
Can add lorazepam PRN, H2RA or PPI
87
Moderate emetic risk chemotherapy regimen
2 or 3 drugs
■ NKl-RA+ 5HT3-RA+ Dexamethasone
- Netupitant or fosnetupitant/palonosetron
■ 5HT3-RA + Dexamethasone
■ Palonosetron + Olanzapine + Dexamethasone
Can add lorazepam PRN, H2RA or PPI
88
Low emetic risk chemotherapy regimen
1 drug (any except NK1-RA)
■ 5HT3-RA (olasetron, granisetron ar ondansetron)
■ Dexamethasone
■ Prochlorperazine
■ Metoclopramide
89
What Antiemetics can u give for Breakthrough CINV
- 5HT3-RAs
- dopamine receptor antagonists
- cannabinoids
- olanzapine
- lorazepam
- dexamethasone
- scopolamine
90
most common SE of 5HT3-RA
- Usually well-tolerated by most patients
- Migraine-like headaches
- Constipation being common side effects.
- Minimal sedation compared to dopamine receptor antagonists and cannabinoids.
91
1) What drugs are dopamine receptor antagonists
2) SE
3) how can you treat the SE
1) Prochlorperazine, promethazine and metoclopramide
2) Pts might experience
- Sedation
- some anticholinergic side effects
- Extrapyramidal symptoms (EPS) such as acute dystonic reactions can occur, especially in younger patients.
3) Acute dystonic reactions should be treated with anticholinergics (benztropine, diphenhydramine).
92
1) what is droperidol
2) why is it not used much? main SE?
3) where do we commonly use it?
- Droperidol is an antiemetic in the same class as haloperidol (i.e., butyrophenones).
- Droperidol has restricted use (or has been removed entirely) in most hospitals due to QT-prolongation and the risk of Torsades de Pointes.
- Droperidol used to be commonly used for postoperative nausea and vomiting (not for CINV).
93
MOA of Substance P/Neurokinin-1 Receptor Antagonist:
inhibit the substance P/neurokinin 1 receptor, therefore augmenting the antiemetic activity of 5HT3 receptor antagonists and corticosteroids to inhibit acute and delayed phases of chemotherapy-induced emesis
94
Aprepitant brand names
dosage forms?
- Emend PO
- EmendTri-Pack
- Cinvanti (Injection)
Capsule, injection (Cinvanti), suspension
95
Aprepitant dosing regimen?
PO: 125 mg 1 hour before chemo on day 1, then 80 mg daily x 2 days
96
Fosaprepitant Band names
dosage forms?
Emend IV
97
Fosaprepitant dosing regimen
IV: 150 mg 30 minutes before chemo
98
Akynzeo active ingredient (PO/IV?)
dosing regimen?
Netupitant + palonosetron (PO)
PO: 300/0.5 mg 1 hour before chemo
Fosnetupitant + palonosetron (IV)
IV: 235/0.25 mg 1 hour before chemo
99
Rolapitant brand name?
dosage form?
dosing regimen?
Varubi
Tablet, injection
PO: 180 mg 1-2 hours before chemo
100
contraindications:
- Aprepitant/fosaprepitant
- Rolapitant
- Aprepitant/fosaprepitant:
do not use with pimozide or cisapride (CYP3A4 substrates)
- Rolapitant:
do not use with thioridazine or pimozide (CYP2D6 substrates)
101
se of nk1ra
- Dizziness,
- fatigue,
- constipation,
- weakness,
- hiccups
- Fosaprepitant: infusion site reactions
102
what should you do to dexamethasone dose when used concurrently with
- Aprepitant/fosaprepitant/netupitant
- Rolapitant
Aprepitant/fosaprepitant/netupitant
decrease dexamethasone dose (CYP3A4 substrate) when used concurrently as an antiemetic
Rolapitant is a CYP2D6 inhibitor; dose of dexamethasone should not be decreased when used concurrently as an antiemetic
103
moa of 5HT-3 Receptor Antagonists
- Work by blocking serotonin, both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone.
- All may be given once prior to chemotherapy on day 1, with the exception of the granisetron transdermal)
patch which is started prior to day 1 of chemotherapy.
104
Ondansetron
brand names
Doses
- Zofran
- Zuplenz film
PO: 8 - 24 mg
IV: 8 - 16 mg
105
Granisetron
brand names
Doses
- Sancuso
- Sustol
- PO: 1-2 mg
- IV: 10 mcg/kg or 1 mg
- SC (Sustol): 10 mg over 20-30 seconds
- Patch (Sancuso):.3.1 mg/24 hour, apply 24-48 hours before chemo; may leave in place up to 7 days
106
Palonosetron brand?
+ netupitant (brand?)
+ fosnetupitant (brand?)
dose?
Palonosetron (Aloxi)
+ netupitant (Akynzeo)
+ fosnetupitant (Akynzeo)
- IV (Aloxi): 0.25 mg
- PO (Akynzeo): 0.5/300 mg 1 hour before chemo
- IV (Akynzeo): 0.25/235 mg 1hour before chemo
Palonosetron PO only available in combination with netupitant (Akynzeo)
107
Dolasetron brand?
dose?
Anzemet
PO: 100 mg
IV: Not indicated for CINV due to i risk for QT prolongation
108
can a pt take apomorphine with any 5ht3 antagonist? why?
Contraindication: Do not use with apomorphine (Apokyn) due to severe hypotension and loss of consciousness.
109
3 warnings with 5ht3 antagonists:
1) Dose-dependent inc in QT interval (Torsades de Pointes) - more common with IV
2) Serotonin syndrome when used in combination with other serotonergic agents
3) Constipation, progressive ileus and gastric distension (Sustol)
110
side effects with 5ht3 antagonists
1) Headache,
2) constipation,
3) fatigue,
4) dizziness,
5) injection site reactions (Sustol)
111
Of the 5HT-3RAs, only ... and ... have FDA-approval for delayed CINV
palonosetron
Sustol
112
Dexamethasone
1) Brand?
2) doses: high/ mod/ low risk
(Decadron)
- All off-label dosing
- High risk: 12 mg PO/IV on day 1 of chemo, then 8 mg PO daily days 2-4
- Moderate risk: 12 mg PO/IV on day 1 of chemo, then 8 mg PO/IV days 2-3
- Low risk: 8-12 mg PO/IV on day/s of chemo
113
CI with CS
- Systemic fungal infections,
- Cerebral malaria
114
SE with CS
Short-term side effects include
- Inc appetite/weight gain
- Fluid retention,
- Emotional instability (euphoria, mood swings, irritability, acute psychosis),
- Insomnia,
- GI upset
- Higher doses inc BP and blood glucose (especially in patients with diabetes)
- CS can inc the risk of osteoporosis and bone loss
115
MOA of Dopamine Receptor Antagonists
work by blocking dopamine receptors in the CNS, including the chemoreceptor trigger zone.
116
Prochlorperazine
1) brand?
2) dose?
3) Boxed warning?
1) Compazine, Compro
2)
- 10 mg IV/PO Q6H PRN
- May give 25 mg suppository PRQ12H PRN
3) BBW: inc mortality in elderly patients with dementia- related psychosis.
117
Promethazine
1) brand?
2) dose?
3) Boxed warning?
1) Phenergan, Promethegan
2) 12.5-25 mg PO/IM/IV/PR Q4-6H PRN
3)
- Do not use in children < 2 years of age (risk of respiratory depression).
- Do not give via intra-arterial or SC administration.
- IV route can cause serious tissue injury if extravasation occurs.
- Deep IM injection is preferred.
118
Metoclopramide
1) brand?
2) dosage forms?
3) dose?
4) Boxed warning?
1) Reglan
2) Tablet, ODT, injection
Gimoti nasal spray- diabetic gastroparesis
3) Doses:
- 10-20 mg PO/IV Q4-6H PRN
- highly emetic regimens: 0.5-2 mg/kg/dose PO/IV Q6H PRN
- CrCI < 40 ml/min: give 50% of the dose
4) BBW:
- Tardive dyskinesia (TD) that can be irreversible.
- Discontinue metoclopramide if signs or sx of TD.
- Inc risk of developing TD with inc duration of treatment & total cumulative dose.
- Avoid treatment with metoclopramide for > 12 weeks.
- dec dose with renal impairment.
119
Olanzapine
1) brand
2) dosage form
3) moa
4) dose
5) SE
1) Zyprexa
2) Tablet, ODT, injection
3) Works through several mechanisms (e.g..dopamine, 5HT, histamine)
4) 10 mg PO on the day of chemo, and on days 2-4
5mg PO Q4H PRN, max of 20 mg/day
5) Mild (sedation, orthostasis...) when used for CINV
120
Droperidol
1) Dosage form
2) indication
3) BBW
1) Injection
2) Indicated only for post-operative N/V, NOT FOR CINV
3) BBW
- QT prolongation and serious arrhythmias.
- All patients should have a 12-lead ECG prior to receiving droperidol and continue for 2-3 hours after completing treatment.
- Contraindicated if baseline QT is prolonged.
121
SE of dopamine antagonists
- Symptoms of Parkinson disease may be exacerbated. Avoid use in patients with Parkinson disease
- Sedation, lethargy, hypotension
- Acute EPS (common in children
--> Antidote: diphenhydramine or benztropine
- Can dec seizure threshold
- Neuroleptic malignant syndrome (NMS)
- QT prolongation
- Strong anticholinergic side effects (e.g.,constipation) except with metoclopramide (diarrhea).
122
Cannabinoids
1) MOA
2) SE
1) May work by activating cannabinoid receptors within the central nervous system and/or by inhibiting the vomiting control mechanism in the medulla oblongata.
2) Somnolence, euphoria, inc appetite, orthostatic hypotension, dysphoria, lowering of the seizure threshold, use with caution in patients with histories of substance abuse or psychiatric disorders.
3) Note: Solution contains 50% alcohol.
123
Dronabinol
1) brand
2) class
3) refrigerate or no need?
4) labeled dose?
1) Marinol, Syndros
2) Capsules: C-III
Solution: C-II
3) Refrigerate
4) Labeled dosing: 5mg/m2 PO prior to chemo and Q2-4H after chemo for up to 6 doses/day.
Most patients respond to 5 mg 3-4 times/day.
124
Nabilone
1) brand
2) class
3) refrigerate or no need?
4) labeled dose?
1) Cesamet
2) C-11
3) No refrigeration needed
4) 1-2 mg PO BID, continue for up to 48H after last chemo dose
125
Benzodiazepines
1) MOA
Enhance GABA (an inhibitory neurotransmitter) to decrease neuronal excitability, which results in alleviation of anxiety and suppression of anticipatory nausea and vomiting.
126
Lorazepam
brand
controlled class
dose
Ativan
C-IV
0.5-2 mg PO or IV Q6H PRN
Start the evening prior to
chemotherapy
127
Chemotherapy-induced diarrhea treatment
Antimotility agents:
loperamide and diphenoxylate + atropine,
maximum dose of loperamide is 16 mg/day when treating CID
128
Agents that commonly cause CID that occurs several
days after chemotherapy.
Fluorouracil, capecitabine and irinotecan
Many TKis, especially those targeting VEGF or EGF (sorafenib and sunitinib)
129
The risk of diarrhea is increased when ... is used
in combination with ... or when used in patients
with dihydropyrimidine dehydrogenase (DPD) deficiencies (not common).
fluorouracil (or the prodrug capecitabine)
leucovorin
130
... causes early-onset diarrhea that occurs during the infusion of the drug and is often accompanied by symptoms of cholinergic ... such as ....
Irinotecan
excess
abdominal cramping, rhinitis, lacrimation and salivation.
131
Treatment for cholinergic excess is the anticholinergic drug ...
atropine
132
chemo drugs that can cause mucositis
5-fu, methotrexate
133
is oral mucositis self limiting?
it could be, but sometimes it requires treatment
134
treatment of oral mucositis
viscous lidocaine 2%
magic mouthwash
systemic analgesic
frequent rinsing with NaCl solution (salt water) to retain the moisture
oral mucositis increases the risk of candida infection --> treatment:
nystatin oral suspension
clomitrazole troches
135
how do you administer (Dose) Lidocaine Viscous
BBW?
warning?
SE?
Notes to pt?
2% topical solution for mouth/ throat
15 ml swish and spit/ swallowed Q3H PRN
BBW:
Avoid use in patients < 3 years of age due to reports of seizures, cardiopulmonary arrest and death
Warning:
Exceeding the recommended dose can result in high plasma levels and serious adverse effects (seizures, cardiopulmonary arrest), methemoglobinemia
SE:
Dizziness, drowsiness, confusion, hypotension
Note:
Avoid ingestion of food for 60 minutes following dose due to risk of impaired swallowing and aspiration
136
Pilocarpine
brand
indication
warning
se
notes
Xerostomia
Salagen
5-10 mg PO TIO
Hepatic impairment:
- Moderate: 5 mg BID
- Severe: avoid use
WARNINGS
Use with caution in patients with cholelithiasis, nephrolithiasis, cardiovascular, disease, asthma, bronchitis, COPD
SIDE EFFECTS
Cholinergic side effects: flushing, sweating, nausea, urinary frequency
NOTES
Avoid administering with high-fat meal
137
Chemodrugs that could cause Hand-foot syndrome (erythrodysesthesia)
capecitabine,
fluorouracil,
cytarabine,
liposomal doxorubicin
tyrosine kinase inhibitors (TKis)
sorafenib and sunitinib.
138
HAND-FOOT SYNDROME MANAGEMENT
■ Limit daily activities to reduce friction and heat exposure to hands and feet.
■ Avoid long exposure to hot water (washing dishes, showers). Takeshorter showers in lukewarm water.
■ Avoid use of dishwashing gloves as the rubber will hold in heat.
■ Avoid increased pressure on soles of feet (no jogging, aerobics,
power walking or jumping).
■ Avoid increased pressure on palms of hands (no use of garden tools, screwdrivers, knives for chopping or performing other tasks that require squeezing hand/s on a hard surface).
-Cooling hands/feet with cold compresses provides temporary relief of pain and tenderness.
- Emollients (Aquaphor, Udder cream, bag balm) --> to retain moisture
- Steroids and pain meds --> for inflammation & pain
139
Tumor lysis syndrome (TLS) has occurred with most cancer types, but most commonly occurs with ... and ...
leukemia
non-Hodgkins lymphoma
140
When the cell is lysed, the intracellular components that enter the bloodstream include ...
potassium, phosphate, purines and pyrimidines
141
what does tls cause?
The phosphate that is released into the bloodstream will bind to calcium, which can cause hypocalcemia.
Calcium and phosphate can also precipitate in soft tissues.
TLS causes acute hyperkalemia (which can cause arrhythmias), hyperphosphatemia and hypocalcemia (low serum calcium, in addition to causing anorexia and nausea, can cause seizures) and hyperuricemia.
142
use of xanthine oxidase inhibitor and rasburicase in tls?
usual dose of allopurinol in gout and in tls?
The xanthine oxidase enzyme: convert large amounts of purines into uric acid, causing acute hyperuricemia, which crystallizes, as with gout.
The uric acid crystals damage the kidneys, which can progress to acute renal failure.
Allopurinol is a xanthine oxidase inhibitor that blocks the conversion of purines into uric acid.
The usual initial dose of allopurinol for gout is ~100 mg daily.
For tumor lysis syndrome, higher doses (400 - 800 mg/day) are used and continued for 10-14 days after chemotherapy.
Rasburicase is an expensive medication that is added to allopurinol when allopurinol and hydration fail to control the uric acid level or is not a reasonable option (e.g., with risk of allopurinol-induced rash/severe skin reactions).
Rasburicase converts uric acid to a more water-soluble metabolite (allantoin), which is easily excreted.
Rasburicase is contraindicated in G6PD deficiency. Discontinue immediately and permanently in any patient developing hemolysis.
Both allopurinol and rasburicase are initially given with IV normal saline (NS), which increases urine output to speed up excretion of some of the excess intracellular components.
143
what happens in HYPERCALCEMIA OF MALIGNANCY
how can you treat them?
what level of calcium is considered mod/severe? sx?
how do you treat it
Certain cancers cause calcium to leach from bone, causing hypercalcemia and bones that are weak and prone to fracture.
hydration and loop diuretics
Moderate to severe hypercalcemia (calcium > 12 mg/dL) is symptomatic, with nausea, vomiting, fatigue, dehydration and confusion.
Treatment includes IV hydration with normal saline and medication to lower calcium levels.
144
Hydration with normal saline and loop diuretics
moa
onset
degree of hypercalcemia
- inc renal calcium excretion
- min to hrs
- Mild (oral or IV hydration) Moderate
Severe
145
Calcitonin
- brand
- dose
- moa
- onset
- degree of hypercalcemia
- Miacalcin
- 4-8 units/kg IM/SC Q12H
- Inhibits bone resorption, inc renal calcium excretion
- 2-6 hours
- Moderate/ Severe
146
IV Bisphosphonates
Zoledronic acid:
Pamidronate
moa
onset
degree of hypercalcemia
Zoledronic acid:
- Zometa
- 4 mg IV once, may repeat in 7 days if needed.
- Do not infuse over < 15 minutes due to increased risk of renal toxicity.
- Dose does not need to be adjusted for mild-moderate renal insufficiency when used for hypercalcemia.
(Do not confuse with Reclast, which is dosed at 5 mg IV yearly for osteoporosis)
Pamidronate
- 60-90 mg IV over 2-24 hrs once, may repeat in 7 days if needed.
MOA: Inhibits bone resorption by stopping osteoclast function
Onset: 24-72 hours
Mild/ Moderate/ Severe
147
Denosumab
-brand
-dose
- moa
- onset
- degree of hypercalcemia
- Xgeva
- 120 mg SC on days 1, 8 and 15 of the first month, then monthly
(Do not confuse with Prolia which is dosed at 60 mg SC every 6 months for osteoporosis
-Monoclonal antibody that blocks the interaction between RANKL and RANK (a receptor on osteoclasts), preventing osteoclast formation
- 24 - 72 hours
- mod - severe
148
Degree of hypercalcemia:
- mild
- mod
- severe
corrected calcium formula
- Mild: corrected calcium< 12 mg/dL,
- Moderate: corrected calcium 12-14 mg/dL,
- Severe:corrected calcium> 14 mg/dL,
or presence of symptoms.
Corrected Calcium (mg/dL) =Calcium (reported)+ /(4 - Albumin) x 0.8}
