61. Oncology I: Overview + Side Effect Management Flashcards
Types of skin cancers and differences
Basal cell and squamous cell carcinoma - common, unlikely to metastasize, simple to remove surgically or with topical treatment
Melanoma - skin cancer that forms in the melanocytes, least prevalent type of skin cancer (2%) but most deadly
Define adjuvant
Treatment given AFTER primary therapy (usually surgery) or CONCURRENT with other therapy (usually radiation) to eradicate residual disease and decrease recurrence
___ results are used to make a definitive cancer diagnosis
Biopsy
Define metastatic
Term for cancer that has spread to a different part of body from primary (starting) location
Define neoadjuvant
Treatment given BEFORE primary therapy (usually surgery) to shrink size of tumor and make surgery more effective
Radiation therapy uses high-energy ___ or other particles to destroy cancer cells
X-rays
Define remission
Disappearance of s/sx of cancer but not necessarily the presence of the disease (cancer could be undetectable but still present)
What does T, N, and M stand for in the TNM staging
T - tumor size and extent
N - spread of cancer to lymph notes
M - whether cancer has metastasized
____ test is one type of tumor marker common in colon cancer
Carcinoembryonic antigen (CEA)
Metastases form when malignant cells from the primary cancer (original site) travel through the ___ or ___ to form new tumors in other parts of the body
Lymphatic system or blood
The American Cancer Society (ACS) lists 7 warning signs (CAUTION). What are they?
Change in bowel or bladder habits
A sore that does not heal
Unusual bleeding or discharge
Thickening or lump in breast or elsewhere
Indigestion or difficulty swallowing
Obvious change in wart or mole
Nagging cough or hoarseness
____ is recommended for prevention of colorectal cancer
Low-dose aspirin
To lower skin cancer risk, use a broad-spectrum sunscreen, at least SPF ___, and reapply every ___ hours
SPF 30, every 2 hrs
Breast cancer screening recommendations
40-44yo: optional annual mammograms
45-54yo: begin yearly mammograms
≥55yo: mammograms every 2 years or continue yearly
Cervical cancer screening recommendations
25-65yo
Pap smear every 3 years
HPV testing every 5 years
PAP smear + HPV testing every 5 years
Colorectal cancer screening recommendations
≥45 yo
Stool-based test (fecal occult blood test (gFOBT) yearly // stool DNA test (MT-sDNA) every 3 years)
Colonoscopy every 10 years
Sigmoidoscopy (FSIG) every 5 years
Lung cancer screening recommendations
≥50yo
Annual CT scan of chest if smoking hx + still smoking or quit smoking within past 15 years
Prostate cancer screening recommendations
If patient chooses to be tested:
Prostate-specific antigen (PSA) blood test ± digital rectal exam (DRE)
T/F: Female pts on chemotherapy should avoid pregnancy during treatment, no teratogenic concern in male pts
False - all pts regardless of gender must avoid conceiving during treatment
T/F: Pregnant females should not handle chemotherapy drugs
True
Max dose and reason: Bleomycin
Lifetime cumulative dose: 400 units
Pulmonary toxicity
Max dose and reason: Doxorubicin
Lifetime cumulative dose: 450-550 mg/m2
Cardiotoxicity
Max dose and reason: Cisplatin
Dose per cycle not to exceed 100 mg/m2
Nephrotoxicity
Max dose and reason: Vincristine
Single dose “capped” at 2 mg
Neuropathy
An IV room pharmacist might dispense a drug that requires a chemoprotectant (i.e., a medication to limit toxicity, such as ___ to prevent cardiac damage from ____)
Dextrazoxane
Doxorubicin
Almost all chemotherapy drugs cause myelosuppression except ____
Asparaginase, belomycin, vincristine, most monoclonal antibodies (MAbs)
Management of chemotherapy-associated neutropenia
Colony-stimulating factors (CSFs)
Management of chemotherapy-associated anemia
RBC transfusions, and (in palliation only) erythropoiesis-stimulating agents (ESAs)
Management of chemotherapy-associated thrombocytopenia
Platelet transfusion (when very low, especially if bleeding)
Chemotherapy drugs that cause N/V
Cisplatin, cyclophosphamide, ifosfamide
Others: doxorubicin, epirubicin
Management of chemotherapy-associated N/V
NK1-RA, 5HT3-RA, dexamethasone, IV/PO fluid hydration
Others: olanzapine, metoclopramide, prochlorperazine
Chemotherapy drugs that cause mucositis
Flurouracil, methotrexate
Others: capecitabine, irinotecan, many TKIs
Management of chemotherapy-associated mucositis
Symptomatic treatment (e.g. mucosal coating agents, topical local anesthetics (such as viscous lidocaine)) and analgesics for pain
Chemotherapy drugs that cause diarrhea
Irinotecan, capecitabine, fluorouracil, methotrexate, many TKIs
Management of chemotherapy-associated diarrhea
IV/PO fluid hydration, antimotility medications (e.g. loperamide)
Irinotecan: atropine for early-onset diarrhea
Chemotherapy drugs that cause constipation
Vincristine
Others: pomalidomide, thalidomide
Management of chemotherapy-associated constipation
Stimulant laxatives, PEG (PEG3350, Miralax)
Management of chemotherapy-associated xerostomia
Artificial saliva substitutes, pilocarpine, amifostine
Chemotherapy drugs that cause cardiomyopathy
Anthracyclines
Others: HER2 inhibitors (adotrastuzumab, trastuzumab, pertuzumab, lapatinib), fluorouracil
Management of chemotherapy-associated cardiomyopathy
Do not exceed lifetime cumulative dose of 450-550 mg/m2 for doxoruicin; give dextrazoxane ppx in select pts receiving doxorubicin
Chemotherapy drugs that cause QT prolongation
Arsenic trioxide, many TKIs, leuprolide
Chemotherapy drugs that cause pulmonary fibrosis
Bleomycin, busulfan, carmustine, lomustine
Chemotherapy drugs that cause pneumonitis
MAbs targeting CTLA-4 or PD-1/PD-L1, methotrexate
Management of chemotherapy-associated pulmonary toxicity (pulmonary fibrosis or pneumonitis)
Steroid for immunotherapy agents
Do not exceed lifetime cumulative dose of 400 units for bleomycin
Symptomatic management
Stop therapy
Chemotherapy drugs that cause hepatotoxicity
Antiandrogens (bicalutamide, flutamide, nilutamide)
Others: folate antimetabolites (e.g. methotrexate), pyrimidine analog antimetabolites (e.g. cytarabine), many TKIs, some MAbs
Management of chemotherapy-associated hepatotoxicity
Steroids for immunotherapy agents (e.g. CTLA-4 or PD-1/PD-L1 immune therapy MAbs - atezolizumab, durvalumab, ipilimumab, nivolumab, and pembrolizumab)
Consider stopping therapy
Symptomatic management
Chemotherapy drugs that cause nephrotoxicity
Cisplatin, methotrexate (high doses)
Others: memtrexed, pralatrexate, some MAbs)
Management of chemotherapy-associated nephrotoxicity
Amifostine (Ethyol) can be given ppx with cisplatin to reduce risk of nephrotoxicity
Ensure adequate hydration
Do not exceed max dose 100mg/m2/cycle for cisplatin
Chemotherapy drugs that cause hemorrhagic cystitis
Ifosfamide (all doses), cyclophosphamide (higher doses > 1g/m2)
Management of chemotherapy-associated hemorrhagic cystitis
Mesna (Mesnex) is ALWAYS given ppx with ifosfamide (and sometimes with cyclophosphamide) to reduce risk of hemorrhagic cystitis
Ensure adequate hydration
Chemotherapy drugs that cause peripheral neuropathy
Vinca alkaloids (vincristine, vinblastine, vinorelbine)
Platinums (cisplatin, oxaliplatin)
Taxanes (paciltaxel, docetaxel, cabazitaxel)
Others: proteasone inhibitors (bortezomib, carfilzomib), thalidomide, ado-trastuzumab emtansine, cytarabine (high doses, brentuximab)
Management of vincristine-associated neuropathy
Limit dose of vincristine to 2 mg per dose (Regardless of BSA calculated dose)
Management of oxaliplatin-associated neuropathy
Causes an acute cold-mediated sensory neuropathy; instruct pts to avoid cold temps and avoid drinking cold beverages
Chemotherapy drugs that cause thromboembolic risk (clotting)
Aromatase inhbitors (e..g anastrozole, letrozole), SERMs (e.g. tamoxifen, raloxifene)
Others: immunomodulators (thalidomide, lenalidomide, pomalidomide)
Treatment and Indication for adjunctive therapy for cisplatin
Amifostine (Ethyol) and hydration
Ppx to prevent nephrotoxicity
Treatment and Indication for adjunctive therapy for doxorubicin
Dexrazoxane (Totect, Zinecard)
Ppx to prevent cardiomyopathy
Treatment and Indication for adjunctive therapy for fluorouracil
Leucovorin or levoleucovorin
To enhance efficacy (as a cofactor)
Treatment and Indication for adjunctive therapy for fluorouacil or capecitabine
Uridine triacetate
Antidote: use within 96 hrs for an overdose or to treat severe, life-threatening or early-onset toxicity
Treatment and Indication for adjunctive therapy for ifosfamide
Mensa (Mesnex) and hydration
Ppx to prevent hemorrhagic cystitis
Treatment and Indication for adjunctive therapy for irinotecan
Atropine - prevent or treat acute diarrhea
Loperamide - to treat delayed diarrhea
Treatment and Indication for adjunctive therapy for methotrexate
Leucovorin or levoleucovorin - ppx to protect cells from toxicity (e.g. myelosuppression, mucositis) after high-dose methotrexate
Glucarpidase - antidote; use within 48-60 hrs for pts with methotrexate induced AKI and delayed methotrexate clearance
S/sx and treatment of chemotherapy-associated anemia
decreased RBCs (Hgb/Hct)
Weakness/fatigue
Can resolve on its own or with RBC transfusion
ESA (Epotein alfa (Epogen, Procrit) or Darboepoetin alfa (Aranesp)
S/sx and treatment of chemotherapy-associated thrombocytopenia
Decreased platelets
Bleeding
Platelet transfusion if platelets very low <10,000 cells/mm3
S/sx and treatment of chemotherapy-associated leukopenia
Decreased WBC (immune response)
Fever/infection
Colony-stimulating factor (CSF): filgastrin (Neupogen), pegfilgrastim (Neulasta)
The lowest point that WBCs and platelets reach is called the ___ which occurs (With most drugs) about 7-14 days after chemotherapy
nadir
The RBC nadir is much later than WBC/platelet nadir, about ___ days, d/t long lifespan of RBCs
120 days
WBCs and platelets generally recover ___ weeks post treatment. The next dose of chemotherapy is given after WBCs and platelets have returned to a safe level (may be delayed for more time to recover).
3-4 weeks
T/F: WBCs and platelets recovery should be done naturally. Use of drugs or transfusions is not recommended.
False - Drugs that hasten recover can be needed. Severe cases can require a transfusion (e.g. giving RBCs for severe anemia)
Neutropenia is defined as ANC < ____ while severe neutropenia is ANC < ____
Neutropenia = ANC <1000
Severe neutropenia = ANC <500
Role of growth colony-stimulating factors in myelosuppression
Stimulate production of WBCs, given ppx after chemotherapy to shorten time that a pt is at risk for infection d/t neutropenia and reduce mortality from infections
Prevent neutropenia
Filgrastim (Neupogen) vs Pegfilgrastim (Neulasta) dosing schedule
Filgrastim = daily
Pegfilgrastim = once per chemo cycle (longer half-life); must document when given, should have at least 14 days before next chemotherapy cycle
____ is the colony-stimulating factors med used most commonly for stem cell transplants
Sargramostim (Leukine)
Side effects of Filgrastim/pegfilgrastim
Bone pain
Others: fever, glomerulonephritis, generalized rash, injection site reaction
Side effects of sargramostim
Fever, bone pain, arthralgias, myalgias, rash
Others: dyspnea, peripheral edema, pericardial effusion, HTN, chest pain
Storage for Colony-stimulating factors
Store in refrigerators, protect vials and syringes from light
When using colony-stimulating factors, pts should report any signs of _____
enlarged spleen (pain in left upper abdomen or respiratory distress syndrome)
Febrile neutropenia diagnosis requirements
Fever: oral temp ≥ 38.3ºC (101ºF) x1 reading (or ≥ 38ºC (100.4ºF) sustained for >1 hr)
Neutropenia: ANC < 500 (or ANC <1000 and expected to drop to ≤500 during next 48 hrs)
Both GP and GN bacteria cause infections in febrile neutropenia but ___ bacteria have highest risk of causing sepsis
Gram negative
T/F: In neutropenia, empiric abx are started immediately if a fever occurs
True
Initial empiric abx for febrile neutropenia should include coverage for _____
GN bacteria, including pseudomonas
Empiric abx regimen for febrile neutropenia low risk (expected ANC ≤100 for <7 days, no comorbidities)
PO anti-pseudomonal abx:
Ciprofloxacin or levofloxacin PLUS amox/clav (for adequate GP coverage) or clindamycin (if PCN allergy)
Empiric abx regimen for febrile neutropenia high risk (expected ANC ≤100 for ≥7 days, comorbidities, renal/hepatic impairment)
IV anti-pseudomonal beta-lactams:
Cefepime or
Ceftazidime or
Meropenem
Imipenem/cilastatin or
Pip/tazo
Why are erythropoiesis-stimulating agent (ESAs) only used palliatively and not recommended in pts receiving chemotherapy with curative intent?
Can shorten survival and increase tumor progression
What are 4 important things to consider before using ESA in a chemo patient?
Use is only for pts with non-myeloid malignancies where anemia is d/t chemotherapy
Upon initiation, there must be a minimum of 2 additional months of planned therapy
Initiate only when Hgb <10
Use lowest dose to avoid RBC transfusions
____ must be assess since ESAs will not work well to correct anemia if iron levels are inadequate
Serum ferritin, transferrin saturation (TSAT) and total iron-binding capacity (TIBC)
For chemotherapy-induced N/V (CINV), administer antiemetics at least ___ prior to chemotherapy and provide antiemetic medication for breakthrough N/V
30 min
What are the 3 subtypes of chemotherapy-induced N/V (CINV)?
Acute, delayed, and anticipatory
Compare onset of CINV subtypes acute, delayed, and anticipatory
Acute - within 24 hrs after chemotherapy
Delayed - > 24 hrs after chemotherapy
Anticipatory - before chemotherapy
Patient factors that increase risk of chemotherapy-induced N/V (CINV)
Hx of N/V with prior regimens
Female gender, age <50yo, anxiety, depression, dehydration, hx of motion sickness
Drug therapy for acute chemotherapy-induced N/V (CINV)
5HT-3 receptor antgonists (5HT3-RAs)
Others: NK1 receptor antagonist (NK1-RAs), dexamethasone, olanzapine
Drug therapy for delayed chemotherapy-induced N/V (CINV)
NK1-RA, corticosteroids, palonosetron, olanzapine
Others: granisetron ER SC
Drug therapy for anticipatory chemotherapy-induced N/V (CINV)
BZD - start the evening prior to chemotherapy to alleviate anxiety and N/V
Chemo regimens with high emetic risk cause emesis at a frequency > 90%. What is an example of a high emetic risk drug?
Cisplatin
Others: clycophosphamide, ifosfamide
5HT3-RA examples for chemotherapy-induced N/V (CINV)
Dolasetron
Ondansetron
Granisetron
Palonosetron
NK1-RA examples for chemotherapy-induced N/V (CINV)
Aprepitant PO
Aprepitant injectable emulsion IV
Fosaprepitant IV
Rolapitant
Combination antiemetic drug examples for chemotherapy-induced N/V (CINV)
Netupitant/palonosetron PO (Akynzeo)
Fosnetupitant/palonosetrone IV (Akynzeo)
Corticosteroid drug examples for chemotherapy-induced N/V (CINV)
Dexamethasone
For high emetic risk drugs, what antiemetic regimen do you recommend?
3 or 4 drugs:
NK1-RA + 5HT3-RA + olanzapine + dexamethasone (preferred)
Palonosetron + olanzapine + dexamethasone
NK1-RA +5HT3-RA + dexamethasone
Antiemetics for breakthrough chemotherapy-induced N/V (CINV)
5HT3-RAs, dopamine receptors antagonists, cannabinoids, olanzapine
Others: lorazepam, dexamethasone, scopolamine
5HT3-RAs are usually well-tolerated by most pts, with ____ being common side effects
Migraine-like HA and constipation
5HT3-RAs cause minimal sedation compared to ____ and ____
Dopamine receptor antagonists and cannabinoids
Dopamine receptor antagonists such as ____ commonly cause sedation and some anticholinergic side effects. ___ such as acute dystonic reactions can occur, especially in younger patients.
Prochlorperazine, promethazine, and metoclopramide
Acute dystonic reactions should be treated with ___
anticholinergics (benztropine, diphenhydramine)
____ is an antiemetic in the same class as haloperidol (i.e., butyrophenones) but has restricted use (or removed entirely) in most hospitals d/t ____. It used to be commonly used for postoperative N/V (not for CINV)
Droperidol
QT-prolongation (TdP risk)
Cannabinoids such as ___ can be used for refractory N/V. They may cause similar
Dronabinol and nabilone
Side effects of Cannabinoids (dronabinol, nabilone)
Similar to Cannabis - increased appetite, sedation, dysphoria, or euphoria
NK-1RA (aprepitant, fosaprepitant) are CYP___ inhibitors. What changes to dexamethasone dose may needed when used concurrently as an antiemetic?
CYP3A4
Decrease dexamethasone dose (CYP3A4 substrate)
Formulation Aprepitant (Emend) vs fosaprepitant (Emend)
Aprepitant = PO, injection
Fosaprepitant = injection
Contraindications 5HT-3 RA (ondansetron, granisetron, palonosetron)
Do NOT use with apomorphine (Apokyn) d/t severe hypotension and loss of consciousness
Warnings 5HT-3 RA (ondansetron, granisetron, palonosetron)
Dose-dependent prolonged QTc interval (more common with IV)
Serotonin syndrome when sued with other serotonergic agents
Side effects 5HT-3 RA (ondansetron (Zofran, Zuplenz film), granisetron (Sancuso), palonosetron(Aloxi))
HA, constipation
Others: fatigue, dizziness, injection site reactions (Sustol)
Side effects corticosteroids (dexamethasone (Decadron))
Short-term: increased appetite, weight gain, fluid retention, insomnia
Others: emotional instability (euphoria, mood swings, irritability, acute psychosis), GI upset
Long-term: increased BP and blood glucose (esp in pts with DM)
Side effects dopamine receptor antagonists (Prochlorperazine, promethazine (Phenergan), metoclopramide (Reglan), olanzapine (Zyprexa), haloperidol (Haldol)
Sedation, lethargy, acute EPS (common in children; antidote is diphenhydramine or benztropine), can decrease seizure threshold
Others: hypotension, neuroleptic malignant syndrome (NMS), QT prolongation
Boxed warnings for promethazine
Do not use in children < 2yo (risk of respiratory depression)
Do not given via intra-arterial or SC administration, IV route can cause serious tissue injury if extravasation occurs (deep IM injection preferred)
Boxed warnings for metoclopramide
Tardive dyskinesia (TD) that can be irreversible (d/c if occurs)
Decrease dose with renal impairment
Boxed warnings for haloperidol/droperidol
QT prolongation and serious arrhythmias
Warnings for dopamine receptor antagonists (prochlorperazne, promethazine, metoclopramide, olanzapine, haloperidol)
Symptoms of Parkinson disease may be exacerbated - avoid use in Parkinson disease pts
Control schedule of dronabinol capsules vs solution
Capsules = C-III
Solution = C-II
Side effects Cannabinoids (Dronabinol (Marinol), nabilone (Cesamat))
Somnolence, euphoria, increased appetite
Others: orthostatic hypotension, dysphoria, lowering seizure threshold, use with caution in pts with hx of substance abuse or psychiatric disorders
Dronabinol solution contains ___% alcohol
50%
Dronabinol ____ has higher bioavailability than dronabinol ____
oral solution > capsules
2.1 mg solution = 2.5mg capsules
Benzodiazepine MOA in CINV
Enhance GABA (inhibitory NT) to decrease neuronal excitability»_space; alleviation of anxiety and suppression of anticipatory N/V
Antimotility agents such as __ and ___ may be prescribed to treat chemotherapy-induced diarrhea
Loperamide
Diphenoxylate/atropine
The maximum dose of loperamide is ___ /day when treating diarrhea under medical supervision
15mg/day
___ also causes early-onset diarrhea that occurs during infusion of chemo drug and is often accompanied by symptoms of cholinergic excess such as ____. Treatment of cholinergic excess is ___
Irinotecan (I run to the can)
Abdominal cramping, rhinitis, lacrimation, and salivation
Anticholinergic drug atropine
Oral mucositis increases risk of ___
oral Candida infection (thrush)
Hand-food syndrome (aka ___ or PPE) frequently occurs following treatment with ___ and ____
palmar-plantar erythrodysesthesia
capecitabine, fluorouracil
Others: cytarabine, liposomal doxorubicin, and tyrosine kinase inhibitors (TKIs) sorafenib and sunitinib
What changes in electrolytes can tumor lysis syndrome (TLS) cause?
hyperkalemia (can cause arrhythmias), hyperphosphatemia, hypocalcemia (can cause seizure, anorexia, nausea), and hyperuricemia
Allopurinol is a ___ inhibitor that blocks the conversion of purines into uric acid. Treatment for TLS requires higher doses than gout.
xanthine oxidase
If allopurinol is not reasonable option (e.g. risk of allopurinol-induced rash/severe skin reactions), ___ can be used as alternative
febuxostat
___ is used for initial management of TLS for patients at high risk (e.g. WBC >100,000, Burkitt Lymphoma). Converts uric acid to more water-soluble metabolite which is easily secreted
Rasburicase
Rasburicase (used in TLS management for pts at high risk) is contraindicated in ___ deficiency
G6PD
Certain cancers cause calcium to leach from bone and into the blood cause ____ which can lead to weak bones (fractures)
hypercalcemia
Pts with mild hypercalcemia (corrected calcium < ___) do not require immediate treatment though ___ can be considered
<12
hydration
___ is generally considered first-line for hypercalcemia of malignancy. In severe cases, ___ may be added (for up to 48 hrs, d/t tachyphylaxis (tolerance)).
___ may be used for hypercalcemia refractory to first line therapy
IV bisphosphonate (e.g. pamidronate, zoledronic acid)
Calcitonin
Denosumab
Zoledronic acid: Zometa vs Reclast
Reclast - IV yearly for osteoprorosis
Zometa - IV once, may repeat in 7 days if needed for hypercalcemia of malignancy
Denosumab: Xgeva vs Prolia
Prolia - SC every 6 months for osteoporosis
Xgeva - SC on days 1, 8, 15 of first month, then monthly for hypercalcemia of malignancy
MOA of denosumab (Xgeva)
Monoclonal antibody that blocks interaction between RANKL and RANK (a receptor on osteoclasts), preventing osteoclast formation
______ commonly occur with virtually every monoclonal antibody (MAb). ___ can be used to prevent it
Immunologic reactions
Premedication - APAP and diphenhydramine ± steroids
T/F: many chemotherapy agents are vesicants
True
Major chemotherapy vesicants include ___ and ___
anthracyclines
Vinca alkaloids
If extravasation occurs, apply (warm/cold) compresses
Exception: with vinca alkaloids and etoposide use (warm/cold) compresses
cold
warm
Antidote of Drug extravasated: anthracyclines
dexrazoxan or dimethyl sulfoxide
Antidote of Drug extravasated: vinca alkaloids and etoposide
Hyaluronidase
Which chemotherapy drugs can be given intrathecally (into CSF)?
Cytarabine, methotrexate, hydrocortisone and thiotepa
Must be preservative-free
T/F: pts currently on chemotherapy should receive vaccinations
False- should avoid during chemotherapy
Vaccination should precede chemotherapy by ≥ 2 weeks
