Oncology

Question 1

Cancer causes

Answer 1

1. Genetic Mutations
   -Proto-oncogenes: involved in normal cell division, but are mutated to oncogenes that promote cancer cell growth (ex. HER2, EGFR)
   -DNA repair genes: mutatations prevent fixing of mistakes
   -Tumor suppressor genes: normally regulate cell division, but then are mutated to let cells grow uncontrollably (ex. BRCA1/2)
2. External Factors
   -Lifestyle: tobacco use, excessive alcohol intake, poor diet, low physical exercise
   -Environmental exposure: sunlight, chemicals (benzene, formaldehyde), radiation, viruses
3. Internal Factors - hormones, older age, inherted gentic mutations

Question 2

Cancer Prevention Methods

Answer 2

1. Avoid tobacco
2. Limit alcohol intake
3. Maintain healthy lifestyle
4. Receive certain vaccinations (ex. HPV)
5. Low-dose ASA in select pts for colorectal cancer prevention
6. Regular check-ups to assess cancer risk, family hx, and individual hx and getting regular cancer screenings
7. Skin protection and screening for abnormal spots

Question 3

Skin Cancer: risk factors, how to protect skin, and how to screen skin

Answer 3

Risk factors: UV light exposure (sun or tanning beds), light skin that burns easily, light hair color, skin cancer hx, immunosuppressive drugs or diseases

Skin protection:
-Seek shade, especially between 10am-4pm
-Wear a shirt (tightly woven fabrics are best)
-Use broad-spectrum sunscreen at least SPF 30 and reapply Q2H (more frequently if swimming or sweating)
-Wear a hat (w/ 2-3’’ brim)
-Wear sunglasses to protect skin around eyes

Screening: ABCDE
-A: Asymmetry
-B: Border (ireggular and notched)
-C: Color (multiple)
-D: Diameter (larger than 6mm or size of tip of pencil eraser)
-E: Evolving (changing in size, color, or symptoms present - bleeding and itching)

Question 4

Colorectal Cancer Screening:
-Age
-Types of tests that can be done

Answer 4

Age: 45 yo and older M/F

Stool-based tests:
-Highly sensitive fecal immunochemical test (FIT) yearly
-Highly sensitive guaiac-based fecal occult blood test (gFOBT) yearly
-Multi-targeted stool DNA test (MT-sDNA) Q3 years

Visual exams of colon and rectum:
-Colonoscopy Q10 years (and PRN to confirm results from other tests)
-CT colongraphy (virtual colonoscopy) Q5 years
-Flexible sigmoidoscopy (FSIG) Q5 years

Question 5

For each cancer, list the screening recommendations
-Breast
-Cervical

Answer 5

Breast:
-40-44 yo F: annual mammogram is optional
-45-54 yo F: yearly mammogram
-55 yo and older F: mammogram Q2 years or continue yearly

Cervical: 25-65 yo F –> pap smear Q3 years, HPV DNA test Q5 years, or pap smear + HPV DNA test Q5 years

Question 6

For each cancer, list the screening recommendations:
-Lung
-Prostate

Answer 6

Lung: 50 yo or older M/F: annaul low-dose CT scan of chest IF both criteria are met:
1. At least 20 pack-year smoking hx
2. Still smoking or quit smoking within past 15 years

Prostate: individualized decision in men using either prostate-specific antigen (PSA) blood test +/- digital rectal exam (DRE)

Question 7

What are the warning signs of cancer (CAUTION)?

Answer 7

-C: Change in bowel or bladder habits

-A: A sore that does not heal

-U: Unusual bleeding or discharge

-T: Thickening or lump in breast or elsewhere

-I: Indigestion or difficulty swallowing

-O: Obvious change in wart or mole

-N: Nagging cough or hoarseness

Question 8

Define the following cancer terminology:
-Benign
-Malignant
-Carcinoma
-Leukemia
-Lymphoma
-Multiple myeloma
-Sarcoma

Answer 8

Benign: non-cancerous

Malignant: cancerous which can metastasize

Carcinoma: forms from epithelial celsl that line internal and external surfaces of body

Leukemia: originates in the bone marrow and usually affects leukocytes

Lymphoma: begins in cells of lymphatic system

Multiple myeloma: arises from plasma cells of bone marrow

Sarcoma: develops in connective or supportive tissue (ex. muscle, bone, cartilage)

Question 9

Define the following cancer treatment terminology:
-Neoadjuvant therapy
-Adjuvant therapy
-Complete response
-Partial response

Answer 9

Neoadjuvant therapy: used prior to surgery to shrink the tumor and make complete resection more likely (ex. chemotherapy, radiation)

Adjuvant therapy: additional cancer treatment given after primary treatment (surgery) to eradicate residual disease and decrease recurrence

Complete response: cancer cannot be detected after therapy

Partial response: substantial reduction in cancer burden, but still present

Question 10

Cancer Staging: TNM

Answer 10

T: tumor size
N: node status
M: metastatis

Higher the number, more advanced cancer is

Question 11

Chemotherapy: list the agents for each category and what each phase dose
-Cell cycle nonspecific
-G0 phase
-G1 phase
-S phase
-G2 phase
-M phase

Answer 11

Cell cycle nonspecific: tumor killing NOT dependent on phase of cell cycle (“All Awesome Pharmacists”)
-Alkylating agents: cyclophosphamide, ifosfamide
-Anthracyclines: doxorubicin, danorubicin
-Platinum compounds: cisplatin, carboplatin, oxaliplatin

G0 phase: resting phase after mitosis has occurred –> NO drugs that target this phase since they target actively dividing cells

G1 phase: growth phase to prepare DNA, RNA, and proteins for cell division: pegasprgase

S phase: DNA replication:
-Folate antimetabolites: methotrexate, pemetrexed
-Pyrimidine analog antimetabolites: fluorouracil (5-FU), capecitabine
-Topoisomerase I Inhibitors: irinotecan, topotecan

G2 Phase: another growth phase to prepare for cell division: etoposide, bleomycin

M Phase: mitosis (cell division)
-Taxanes: paclitaxel, docetaxel
-Vinca alkaloids: vincristine, vinblastine

Question 12

Where are rapdily dividing cancer cells typically located, and why is this important in context of chemotherapy agents?

Answer 12

Found in GI tract, hair follicles, and bone marrow –> thus why chemotherapy often casues diarrhea, mucositis, N/V, alopecia, and myleosuppression

Drugs often given in 2-6 week cycles followed by days or weeks w/o chemotherapy to allow recovery from these side effects

Question 13

Chemotherapy calculations:
-Mostellar Equation
-Du bois and Du bois Equation
-Calvert Formula

Answer 13

Mosteller: BSA(m2) = square root [(ht in cm x wt in kg)/3600]

Du bois: BSM(m2) = 0.007184 x (Ht in cm)^0.725 x (Wt in kg)^0.425

**Mostellar and Du bois is used to caclulate most chemotherapy dosing –> use PT’s ACTUAL WEIGHT

Ca;vert: used for carboplatin dosing
-Total carboplatin dose (mg) = target AUC x (GFR + 25)
-AUC can range from 2-8 mg/mL x min
-GFR is most commonly capped at 125mL/min/1.73m2
-Creatine clearance may be used to estimate GFR if NOT provided

Question 14

Cyclophosphamide:
-Brand
-MOA
-Safety concerns
-Monitoring
-Management

Answer 14

Brand: Cytoxin

MOA: alkylating agent that cross-links DNA strands to inhibit DNA and protein synthesis, resulting in cell death (nonspecific cell cycle agent)

Safety Concerns: HEMORRHAGIC CYSTITIS (caused from toxic metabolite acrolein which concentrates in the bladder which releases pro-inflammatory phases)

Monitoring: HEMATURIA, urinalysis (for RBCs), lower urinary tract symptoms (urinary urgency, DYSURIA, incomplete bladder emptying)

Management:
-Adequate HYDRATION (helps flush bladder and excretion of acrolein)
-MESNA: binds and inactivates acrolein, should be started before chemotherapy (chemoprotectant w/ high doses >1gram/m2)
-Bladder irrigation w/ NS

Question 15

Ifosfamide
-Brand
-MOA
-Safety concerns
-Monitoring
-Management

Answer 15

Brand: Ifex

MOA: alkylating agent that cross-links DNA strands to inhibit DNA and protein synthesis, resulting in cell death (nonspecific cell cycle agent)

Safety Concerns: neurotoxicity, including encephalopathy and cerebellar dysfunction, HEMORRHAGIC CYSTITIS (caused from toxic metabolite acrolein which concentrates in the bladder

Monitoring: s/sx of neurotoxicity (confusion, incoordination, imbalance), HEMATURIA, urinalysis (for RBCs), lower urinary tract symptoms (urinary urgency, DYSURIA, incomplete bladder emptying)

Prevention/Treatment: methylene blue for neurotoxicity

Management:
-Adequate HYDRATION (helps flush bladder and excretion of acrolein)
-MESNA: binds and inactivates acrolein, should be started before chemotherapy (ALL doses)
-Bladder irrigation w/ NS

Question 16

Busulfan
-Brand
-MOA
-Safety concerns
-Monitoring
-Management

Answer 16

Brand: Busulfex, Myleran

MOA: alkylating agent that cross-links DNA strands to inhibit DNA and protein synthesis, resulting in cell death (nonspecific cell cycle agent)

Safety Concerns: PULMONARY TOXICITY (pulmonary fibrosis), seizures

Monitoring: s/sx of pulmonary toxicity (dyspnea, cough, pulmonary function tests), s/sx of seizures, HA

Management: symptomatic care (oxygen) for pulmonary toxicity, anticonvulsants

Question 17

Carmustine:
-Brand
-MOA
-Safety Concerns
-Monitoring
-Management

Answer 17

Brand: BiCNU, Gliadel Wafer

MOA: alkylating agent that cross-links DNA strands to inhibit DNA and protein synthesis, resulting in cell death (nonspecific cell cycle agent)

Safety Concerns: NEUROTOXICITY (seizures, cerebral edema) –> particularly with wafer implant (surgically placed in brain for brain tumors); PULMONARY TOXICITY (pulmonary fibrosis)

Monitoring: s/sx seizures, HA, pulmonary toxicity, pulmonary function tests

Prevention/Treatment: symptomatic care (oxygen) for pulmonary toxicity, anticonvulsants

Question 18

Cisplatin
-Brand
-MOA
-Safety Concerns
-Monitoring
-Management

Answer 18

Brand: Platinol

MOA: platinum-based compound that cross-links DNA, interfering with DNA synthesis and cell replication, resulting in cell death (nonspecific cell cycle agent)

Hypersensitivity reactions:
-Monitoring: anaphylaxis (dyspnea, angioedema, urticaria) vital signs (BP, HR)
-TX: symptomatic care (oxygen, bronchodilators, systemic steroids)

Nephrotoxicity:
-Monitoring RENAL function (BUN, SCr, intake/output, electrolyates)
-Prevention: adequate hydration, limit cisplatin dose per cycle to <100mg/m2, amifostine (Ethyol) as chemoprotectant

Ototoxicity:
-Monitoring: s/sx of hearing loss, tinnitus, audiogram at baseline
-Prevention: avoid concomitant ototoxic medications (ex. aminoglycosides)

Peripheral Neuropathy:
-Monitoring: s/sx (extremity numbness, paresthesia, pain)
-TX: symptomatic care (neuropathic pain meds)

Question 19

Compare cisplatin to carboplatin and oxaliplatin

Answer 19

ALL: hypersensitivity rxns, nephrotoxicity, ototoxicity, peripheral neuropathy

Cisplatin: GREASTEST incidence of nephrotoxicity (BBW) and ototoxocitiy

Oxaliplatin: unique side effect of acute sensory neuropathy exacerbated by the cold
-Monitoring: s/sx (abnormal sensations in hands, feet, perioral area, or throat; jaw spasms; chest pressure)
-Prevention: avoid cold exposure (cold temperatures, cold food/beverages)

Question 20

Doxorubicin:
-Brand
-MOA
-Safety Concerns
-Monitoring
-Management

Answer 20

Brand: Adriamycin

MOA: anthracycline that causes intercalation into DNA and inhibits topoisomerase II, inhibiting DNA and RNA synthesis; creates oxygen-free radicals that damage cells (nonspecific cell cycle agent)

Safety Concerns: CARDIOTOXICITY (due to creating radicals), red discoloration of bodily fluids (urine, tears, sweat) –> “-rubi”: ruby

Monitoring: left ventricular ejection fraction (LVEF) before and after, s/sx of HF (edema, SOB), red urine

Prevention:
-Limit total lifetime cumulative dose to 450-550mg/m2 (do NOT exceed lower dose if CV risk present)
-Administer dexrazoxane (chemoprotectant): consider when cumulative doxorubicin dose >/=300mg/m2 and planning to continue TX
-NO preventions for urine discoloration

Question 21

Mitoxantrone:
-Brand
-MOA
-TX
-Safety Concerns
-Monitoring
-Management

Answer 21

Brand: Novantrone

MOA: anthracenedione (related to anthracyclines) that causes intercalation into DNA and inhibits topoisomerase II, inhibiting DNA and RNA synthesis; creates oxygen-free radicals that damage cells (nonspecific cell cycle agent)

Safety concerns: blue discoloration of sclera and bodily fluids

TX: acute nonlymphocytic leukemia, advanced prostate cancer, and MS

Monitoring: blue urine

Management: NO preventions for urine discoloration

Question 22

Irinotecan:
-Brand
-MOA
-Safety Concerns
-Monitoring
-Management

Answer 22

Brand: Camptosar

MOA: topoisomerase I inhibitor that blocks coiling and uncoiling of ds-DNA helix during the S phase of the cell cycle

Safety Concerns:
-ACUTE DIARRHEA (“I run to the can”) during or immediately after infusion + CHOLINERGIC symptoms (abdominal cramping, lacrimation, salivation)
-DELAYED DIARRHEA (>24 hours after infusion): thought to be caused by metabolite that damages colon

Monitoring: frequency of bowel movements, electrolytes, dehydration (dizziness, decreased skin turgor)

Management:
-Atropine for prevention and TX of acute diarrhea (anticholinergic)
-Antidiarrheal (ex. loperamide) for delayed diarrhea
-Both: symptomatic care (hydration, electrolyte replacement)

Question 23

Etoposide:
-MOA
-Safety Concerns
-Monitoring
-Management

Answer 23

MOA: topoisomerase II inhibitor, blocking the coiling and uncoiling of ds-DNA during the G2 phase of the cell cycle

Safety concerns: infusion rate-related hypotension

Monitoring: BP

Management:
-Prevention: infuse over at least 30-60 minutes
-TX: IV hydration, decrease infusion rate upon reinitiation

Question 24

Vincristine, Vinblastine, and Vinorelbine:
-MOA
-Safety Concerns
-Monitoring
-Management

Answer 24

MOA: vinca alkaloids: that inhibit microtubule formation during the M phase of the cell cycle

Safety concerns:
-PERIPHERAL NEUROPATHY (since microtubules play role in axonal transport)
-Autonomic neuropathy (constipation)
-Paralysis and death IF GIVEN INTRATHECALLY (ALWAYS GIVE AS IV)

Monitoring: s/sx of neuropathy (extremity numbness, parasthesia, pain) or constipation (bowel movement frequency, hard stools), double check ROA of product

Management:
-Symptomatic care (neuropathic pain meds, diet modifications, laxatives)
-Prevention of neuropathy: limit single vincristine dose to 2mg (regarldess of BSA calculated dose since causes most peripheral neuropathy of all in class)
-Prevention of paralysis/death: prepare in small IV bag that cannot be used for intrathecal administration, label product

Question 25

Taxanes: -Drugs/Brands -MOA -Safety Concerns -Monitoring -Management

Answer 25

Drugs: paclitaxel (Taxol), cabazitaxel (Jevtana), docetaxel (Taxotere) MOA: inhibit depolymerization of tubulin which would stabilize microtubules during the M phase of the cell cycle Peripheral neuropathy: -Monitoring: s/sx (extremeity numbness, paresthesia, pain) -TX: symptomatic care (neuropathic pain meds) Hypersensitivity rxns (due to solvent symptoms such as polysorbate 80: EXCEPT in albumin-bound paclitaxel - Abraxane) -Monitoring: s/sx of anaphylaxis (dyspnea, uticaria, angioedema), vital signs (BP, HR) -Prevention: premedication w/ systemic steroid (dexamethasone) + Benadryl+ H2RA (famotidine) -TX: D/C therapy (do NOT rechallenge), symptomatic care (oxygen, EPI) Physical Incompatibilities: require non-PVC bags (can leak from PVC bags) -Paclitaxel and cabazitaxel: require 0.22 micron filter Docetaxel: severe fluid retention -Monitoring: s/sx (edema, dyspnea at rest, abdominal distention) -Prevention: premedication w/ systemic steroid (dexamethasone) started the day before and lasting for 3 days total -TX: symptomatic care (diuretics)

Question 26

Fluorouracil (5-FU): -MOA -Safety Concerns -Monitoring

Answer 26

MOA: inhibit pyrimidine DNA synthesis during S phase of cell cycle (pyrmidine analog antimetabolite) - mimics uracil Hand-foot syndrome (palmar plantar erythrodysestheisa) caused by capillary drug leakage into the palms of hands/sores of feet: s/sx (painful erythema, skin peeling) Diarrhea: frequency of bowel movements, electrolytes, dehydration (dizziness, decreased skin turgor) Mucositis: s/sx (painful mouth ulcers, difficulty eating/drinking), s/sx of infection (thrush) Dihydropyrimidine dehydrogenase (DPD) Deficiency: increased risk of severe toxicity (immunosuppression, GI toxicity) Drug interactions w/ warfarin: INR monitoring, s/sx of bleeding (BBW for prodrug, capecitabine)

Question 27

Flurouracil (5-FU): 1. What is the prodrug of 5-FU? 2. What drug is given simultaneously to increase efficacy? 3. What is the antidote of 5-FU toxicities?

Answer 27

1. Capecitabine (Xeloda) 2. Leucovorin (or its L-isomer: levoleucovorin) - stabilizes 5-FU to bind, increasing efficacy 3, Uridine triacetate (Vistogard): within 96 hours for overdose or early-onset toxicity, sympatomic care specific to the toxicity

Question 28

Management of Hand-foot syndrome

Answer 28

1. Limit/modify daily activities to reduce friction/pressure (ex. loose-fitting shoes, avoiding tools that require squeezing) 2. Avoid heat exposure 3. Cold compresses to temporarily relieve pain/tenderness 4. EMOLLIENTS (ex. ammonium lactate, urea cream, Aquaphor) to retain moisture 5. Topical steroids and pain meds to lessen inflammation and pain 6. Dose modifications or therapy interruptions for severe cases (ex. 5-FU)

Question 29

Management of mucositis

Answer 29

Prevention: -Good oral hygiene -Hold ice chips to mouth to cause vasoconstriction to decrease delivery of mucotoxic agent -Frequent rinsing w/ bland rinses (ex. sodium bicarbonate, NaCl solutions) Treatment: -Symptomatic care (viscous lidocaine 2%, magic mouthwash, systemic analgesics for pain) -Parenteral nutrition or IV hydration in certain cases -Thrush treatment (nystatin oral suspension, clotrimazole troches)

Question 30

Cytarabine: -MOA -Safety concerns -Monitoring -Management

Answer 30

MOA: inhibit pyrimidine DNA synthesis during S phase of cell cycle (pyrmidine analog antimetabolite) Safety concerns: neurotoxicity (acute cerebellar toxicity w/ high doses), cytarabine syndrome occuring hours after administration Monitoring: s/sx of neurotoxocity (seizures, slurred speech, confusion, incoordination), s/sx of cytarabine syndrome (fever, weakness, bone pain, chest pain) Management: -Prevention of neurotoxicity: dose modifications for select pts (older age, pre-existing renal/hepatic dysfunction) -Prevention/TX of cytarabine syndrome: systemic steroids (dexamethasone)

Question 31

Methotrexate: -Brand -MOA -Safety Concerns -Monitoring

Answer 31

Brand: Trexall MOA: folate antimetabolite that interferes with enzymes involved in folic acid cycle (inhibits dihydrofolate reductase which converts folic acid to tetrahydrofolate), blocking purine and pyrimidine biosynthesis in S phase of cell cycle Safety Concerns: nephrotoxicity (w/ high doses >/=500mg/m2), GI toxicity (diarrhea, mucositis) Monitoring: renal fxn (BUN, SCr, urine output), weight gain (edema), urine pH (target >/=7 since weak acid), methotrexate levels, s/sx of mucositis (painful mouth ulcers, difficulty eating/drinking), s/sx of infection (thrush)

Question 32

Methotrexate: management of nephrotoxocity

Answer 32

1. Leucovorin or L-isomer (levoleucovorin) as "rescue" for doses >/=500mg/m2 to reduce toxicities --> can ALSO use in GI toxicites 2. Hydration w/ IV sodium bicarbonate to alkalinize the urine (improves methotrexate solubility) 3. Avoid interaction meds (NSAIDs, SALICYCLATES; others: beta-lactams, PPIs, sulfonamide ABXs, probenecid) 4. Caution in pts w/ third spacing (ascites, pleural effusions) which delay drug clearance 5. Antidote: glucarpidase (Voraxaze) which rapidly lowers methotrexate levels by converting it into inactive metbaolites in methotrexate-induced AKI and delayed clearance

Question 33

Methotrexate: between autoimmune and oncologic diseases -What is the typical dose? -What is used in addition to off-set toxicites?

Answer 33

Autoimmune diseases: dose is lower (5-25mg WEEKLY) -Folic acid (folate) 1-5mg QD recommended prophylaxis to reduce side effects (GI, hematologic, hepatic) -Leucovorin NOT used unless unresponse to folic acid Oncologic diseases: doses are higher (>/=40mg/m2 per dose) -Luecovorin or levoleucovorin "rescue" is required for doses >/=500mg/m2 to reduce toxicities (mucositis, diarrhea, nephrotoxicity, myelosuppression) and recommended in 100-500mg/m2--> a reduced folic acid (tetrahydrofolate) that allows DNA synthesis to begin again and replenishing supply of folate metabolites displaced -Folic acid NOT effective for high-dose rescue

Question 34

Tretinoin -MOA/TX of what cancer -Safety concerns -Monitoring -Management

Answer 34

MOA/TX: all trans retinoic acid (ATRA) decreases proliferation and increases differentiation of acute promyelocytic leukemia (APL) cells Safety Concerns: differentiation syndrome (previously known as retinoic acid-acute promyelocytic leukemia RA-APL) syndrome Monitoring: s/sx (fever, dyspnea, weight gain, edema, pulmonary infiltrates, pericardial or pleural effusions Prevention/TX: systemic steroids (dexamethasone), interupt therapy for severe cases

Question 35

Arsenic Trioxide -Brand -MOA -Safety Concerns -Monitoring -Management

Answer 35

Brand: Trisenox MOA/TX: increases apoptosis of acute promyleocytic leukemia (APL) cells and damages fusion protein promyelocytic leukemia-retinoic acid receptor alpha Safety concerns: QT PROLONGATION, differentiation syndrome Monitoring: electrocardiogram, electrolytes, s/sx of differentiation syndrome (fever, dyspnea, weight gain, edema, pulmonary infiltrates, pericardial or pleural effusions) Management: -Qt prolongation: maintain K >4 mEq/L and Mg >1.8 mEq/L, avoid concurrent QT-prolonging drugs -Prophylaxis/TX of differentiation syndrome: systemic steroids (dexamethasone), interrupt therapy for severe cases

Question 36

Bleomycin -Brand -MOA -Safety concerns -Monitoring -Management

Answer 36

Brand: Blenoxane MOA: inhibits DNA synthesis via DNA strand breaks Safety concerns: PULMONARY TOXICITY (BBW), HYPERSENSITIVITY RXNS Monitoring: -Pulmonary: dyspnea, cough, pulmonary fxn tests (prior to TX and periodically during) -S/Sx of anaphylaxis (dyspnea, uticaria, angioedema), vital signs (BP, HR) Management: -Prevention of pulmonary toxicity: LIMIT LIFETIME cumulative dose to 400 units -Hypersensitivity: consider a test dose for the first 2 doses and/or premedication (APAP, Benadryl)

Question 37

Bortezomib and Carfilzomib: -Brand -MOA -Safety concerns -Monitoring -Management

Answer 37

Brand: bortezomib (Velcade), carfilzomib (Kyprolis) MOA: proteosome inhibitor which regulates intracellular protein heomeostasis by inhibiting cell cycle progression HERPES REACTIVATION (zoster and simplex) -Monitoring: s/sx (rash) -Prevention/TX: antivirals (acyclovir, valacyclovir) Peripheral neuropathy -Monitoring: s/sx (extremity numbness, paresthesia, pain) -Prevention: admiinister bortezomib SQ (less neuropathy than IV) -TX: symptomatic care (neuropathic pain meds)

Question 38

Lenalidomide, pomalidomide, and thalidomide: -Brand -MOA -Safety concerns -Monitoring -Management

Answer 38

Brand: lenalidomide (Revlimid), pomalidomide (Pomalyst), thalidomide (Thalomid) MOA: immunomodulators that block angiogenesis (formation of new blood cells) and kill abnormal cells in bone marrow while stimulating the bone marrow to produce normal healthy cells SEVERE BIRTH DEFECTS: -Monitoring: pregnancy test (2 negative required prior to TX) -Prevention: under REMs program (two forms of contraception or abstain from sex) THROMBOSIS (DVT/PE): -Monitoring: s/sx (SOB, chest pain, leg swelling) -Prevention: prophylatic anticoagulant

Question 39

Pegaspargase: -Brand -MOA -Safety Concerns -Monitoring -Management

Answer 39

Brand: Oncaspar MOA: modified form of L-asparaginase (derived from E. coli) conjugated w/ polyethylene glycol which inhibits protein synthesis by depleting aspargine leukemic cells Safety concerns: hypersensitivity rxns (pegylated form allows for less frequent dosing and less allergic rxns) Monitoring: s/sx of anaphylaxis (dyspnea, angioedema, uticaria), vital signs (BP, HR) Management: -Prevention: premedication w/ APAP, antihistamine (Benadryl), and H2RA (famotidine) -TX: symptomatic care (oxygen, EPI)

Question 40

Summary of Chemotherapy Toxicities: ChemoMan -Head -Ears -Mouth -Chest -Heart -Urinary tract -Bone -Extremeties

Answer 40

Head: Neurotoxicity (carmustine) Ears: Otoxocitiy (cisplatin) Mouth: Mucositis (methotrexate, 5-FU, capecitabine, High emetogenicity (cisplatin) Chest: Pulmonary toxicity/pulmonary fibrosis (bleomycin, busulfan, carmustine) Heart: cardiotoxicity/cardiomyopathy (doxorubicin and other antracyclines Urinary tract: hemorrhagic cystitis (ifosfamide and cyclophosphamide), diarrhea (irinotecan) Bones: bone marrow suppression (most chemotherapy EXCEPT bleomycin, pegaspargase, and vincristine) Extremeties: peripheral neuropathy (platinum based-compounds such as oxaliplatin, vinca alkaloids such as vincistine, and taxanes such as placitaxel)

Question 41

Neutropenia from chemotherapy: -ANC calculation and interpretation -Prophylaxis -Febrile neutropenia diagnosis and TX

Answer 41

Absolute Neutrophil COunt: ANC (cells/mm3) = [WBC x (%segs + %bands)] / 100 -Neutrophils: major function to fight infections (lower ANC, higher infection risk) -ANC <1000 cells/mm3: neutropenia -ANC <500 cells/mm3: severe neutropenia -ANC <100cells/mm3: profound neutropenia Prophylaxis: granulocyte colony-stimulating factors (G-CSFs) if pt has high risk of developing febrile neutropenia (based on chemotherapy regimen or comorbidities) Febrile Neutropenia: having a fever (single oral temp >/=101F OR >/=100.4 for >1 hr AND neutropenia (ANC <500 cells/mm3 OR ANC <1000 that is likely to decline to <500 in the next 48 hours) --> RISK OF DEATH due to inability to fight infections -Empiric ABXs started STAT if fever occurs with gram-negative coverage INCLUDING PSUEDOMONAS (highest risk of causing sepsis and death) -High risk: ANC /=7 days, comorbidities: IV anti-pseudomonal beta-lactams (cefepime, ceftazidime, carbopenems except ertapenem, piperacillin/tazobactam) -Low risk: ANC -Post empiric ABXs given, site-specific evaluation followed by treatment modification

Question 42

Myleosuppression: -Define -What chemotherapy drugs do NOT cause myleosuppression? -Explain the process of myleosuppression and recovery

Answer 42

Myleosuppression: decrease in blood cell production, resulting in fewer WBCs (neutropenia), platelets (thrombocytopenia), and RBCs (anemia) do NOT cause: bleomycin, vincristine, and pegaspargase -Typically MABs (monoclonal antibodies) do NOT cause either Myleosuppression Recovery: -After chemotherapy has started, the lowest point of WBCs (nadir) is about 7-14 days after and RBC nadir usually occurs later after several months of TX due to their long life span of 120 days -During nadir period, pt is at greatest risk for compl;ications -General recovery occurs 3-4 weeks after treatment for WBCs and PLTs -Next chemotherapy is started after WBCs especially have returned to safe level and may be delayed to allow more time for recovery

Question 43

Granulocyte Colony-Stimulating Factors (G-CSFs): -Drugs/Brand -MOA -ROA -AVEs -Monitoring

Answer 43

Drugs: filgrastim (Neuopogen), tbo-filgrastim (Granix), pegfilgrastim (Neulasta, Neulasta Onpro), eflapegrastim-xnst (Rolvedon) MOA: stimualate WBC production in bone marrow to shorten duration and severity of neutropenia after chemotherapy -Pegfilgastim: peglyated form with longer T1/2 ROA: SQ (filgrastim can also be IV) AVEs: BONE PAIN, rash, hypersensitivity/allergic rxn (including anaphylaxis), glomerulonephritis, SPLENIC RUPTURE, respiratory distress syndrome Monitoring: CBC w/ differential, vital signs, UPPER ABDOMINAL PAIN

Question 44

What are administration/dosing considerations of granulocyte colony-stimulating factors (G-CSFs)?

Answer 44

Dosing: -Filgrastim: given IV or SQ DAILY until post-nadir recovery -The rest are given ONCE PER CYCLE Administration: 1. Store in refrigerator (protect from light) 2. Administer first dose no sooner then 24 hours after chemotherapy (can be up to 96 hours after) --> chemotherapy could still be lingering in body which would counteract effects of G-CSFs if given 3. Pegfilgrastim: longer T1/2: do NOT administer within 14 days before next chemotherapy cycle; ON-BODY INJECTION applied to abdomen or back of arm after chemotherapy that delivers dose of pegfilgrastim about 27 hours after application

Question 45

Thrombocytopenia due to chemotherapy TX

Answer 45

Low PLTs which can result in spontaneous, uncontrolled bleeding Normal PLT range: 150,000-450,000 cells/mm3 Risk for spontaneous bleeding: PLTs <10,000 cell/mm3 --> platelet infusion indicated Other management: -Chemotherapy dose reduction or delay in therapy -Avoidance of intramuscular injections -Avoidance of medications that affect PLT functioning (NSAIDs)

Question 46

Anemia from chemotherapy: Management

Answer 46

Observation: determine other causes such as folate, vitamin B12, or iron deficiencies -Can resolve w/o TX Symptomatic pts: RBCs transfusions Select pts: erythropoiesis-stimulating agents (ESAs): PALLIATIVE CARE ONLY (can shorten survival/thrombotic events and increase tumor progression) and MUST meet the following criteria: 1. Pt has NON-myleoid maligancny (carcinoma, sarcoma) and anemia is from chemotherapy 2. Hgb <10g/dL and minimum of two additional months of planned chemotherapy 3. The lowest dose to maintain levels is given to avoid RBC transfusions 4. ESA D/C following completion of chemotherapy 5. Pt has iron stores for ESAs to actually work

Question 47

Chemotherapy-Induced Nausea and Vomiting (CINV): 1. Define the different types: acute, delayed, anticipatory, breakthrough, and refractory 2. Who is more at risk for CINV? 3. What drugs are more likely ot cause CINV? 4. Complications

Answer 47

Classifications: -Acute: occurs within 24 hours of chemotherapy and peaks around 5-6 hours -Delayed: occurs >24 hours after chemotherapy -Anticipatory: occurs before TX and develops as a conditioned response from previous negative experience -Breakthrough: occurs at ANY TIME after chemotherapy despite usage of prophylaxis and requires rescue antimetics -Refractory: occurs when propyhalxis and/or rescue TX NOT effective Risk factors: females, younger age, pre-TX anxiety, hx of motion sickness or morning sickness during pregnancy, hx of N/V w/ previous chemotherapy cycles Drugs: most common with CISPLATIN, carboplatin, cyclophosphamide, and anthracyclines Complications: discomfort/reduced QOL, medical complications (esophageal tears, dehydration), TX nonadherence

Question 48

Chemotherapy Induced Nausea and Vomiting (CINV): -General drug classes that can be used -When before chemotherapy do prophylaxis drugs need to be given and how long to give? -Explain what combination of drugs to use for low, moderate, and high emetic risk pts

Answer 48

Drug Classes: 1. Neurokinin-1 receptor antagonists (NK1 RAs): aprepitant, fosaprepitant, rolapitant 2. Serotonin receptor antagonists (5-HT3 RAs): dolasetron, granisetron, ondansetron, palonesetron 3. Dopamine receptor antagonists: olanzapine, haloperidol, metoclopramide, prochlorperazine, promethazine 4. Other: dexamethasone, dronabinol, lorazepam Give drugs at least 30 minutes bofore chemotherapy and continue for the FULL period of emetic risk (ex. if chemotherapy on multiple days, give on all days) High risk in IV (90% frequency of emesis: cipsltain, any regimen containing BOTH anthracycline and cyclophosphamide): 3 or 4 drugs -Preferred: NK1 RA + 5-HT3 RA + olanzapine + dexamethsaone -Alternatively: NK1 RA + 5- HT3 RA + dexamethasone OR paloneosetron + olanzapine + dexamethasone Moderate risk in IV (30-90% frequency): 2 or 3 drugs (NK 1 RA + 5-HT3 RA + dexa OR 5-HT3 RA + dex OR palonosetron + olanzapine + dexa) Low risk in IV (10-30% frequency): one drug (5-HT3, dexa, metoclopramide, or prochlorperazine) Additional add-ons: -Lorazpam for anticipatory N/V -Using other combinations for breakthrough N/V (use DIFFERENT MOAs)

Question 49

Substance P/Neurokinin Recetor Antagonists (NK1 RAs): -Drugs/Brands -ROA -AVEs -Administration -CIs

Answer 49

Drugs: arepitant (Emend, Emend Tri-Pak, Cinvanti), Fosaprepitant (Emend), netupitant/palonesetron (Akynzeo), fosnetupitant/palonosetron (Akynezeo), rolapitant (Varubi) ROA: -IV and PO: aprepitant, palonosetron combos -IV: fosprepitant -PO: rolapitant Adminsitration: -Aprepitant, fosapreiptant, netupitant: inhibit metabolism of dexamethasone (increases levels) -Fosaprepitant IV: converted to aprepitant within 30 minutes after end of infusion -Rolapitant: do NOT administer at leass than 2 week intervals AVEs: generally well tolerated (abdominal pain, dizziness, dyspepsia, fatigue, hiccups, infusion-site rxns) CIs (rolapitant): do NOT use with thioridazine or pimozide (CYP2D6 substrates)

Question 50

5-HT3 Receptor Antagonists: -Drugs/Brands -ROA -Adminsitration -AVEs -Warnings -CIs

Answer 50

Drugs: ondansetron (Zofran). granisetron (Sancuso, Sustrol), palonoestron (Aloxi), dolasetron (Anzemet) ROA: IV and PO (dolasetron PO only), granisetron can be SQ and patch as well Adminsitration: -Sustol (granisetron SQ): do NOT administer more than once Q7 days -Palonosetron: longest T1/2 AVEs: HA, CONSTIPATION, fatigue, dizziness, injection site rxns Warnings: -Hypersensitivity rxns -SEROTONIN SYNDROME (when in combo w/ other serotonergic drugs) -Dose-dependent QT PROLONGATION (more common w/ IV formulations: limit Zofran dose to 16mg, lowest risk w/ palonestron) CI: concurrent use w/ apomorphine (severe hypotension)

Question 51

Dopamine Receptor Antagonists for chemotherapy-induced N/V: -Drugs/Brands -ROA -AVEs -Warnings -BBW

Answer 51

Drugs: olanzapine (Zyprexa), prochlorperazine (Compro), promethazine (Phenergan, Promethagen), metoclopramide (Reglan), haloperidol (Haldol) ROA: all PO -IV: prochlorperazine, metoclopramide, haloperido -PR: prochlorperazine, promethazine AVEs: SEDATION, LETHARGY, ACUTE EXTRAPYRAMIDAL SYMPTOMS or AES (antidote: Benadry or benztropine), QT PROLONGATION, decrease seizure threshold, hypotension, neuroleptic malignant syndrome (NMS) -Strong anticholinergic side effects (consitpation) except w/ metoclopramide (prokinetic effect causes diarrhea) Warnings: avoid use in Parkinson disease (exacerbation BBW: -Olanzapine, prochlorperazine, haloperidol: increased mortality in elderly pts w/ dementia-related psychosis -Promethazine: do NOT use in children UNDER 2 YEARS OLD (respiratory depression); can cause serious tissue injury due to EXTRAVASATION if administered intra-arterially, SQ, or IV -Metoclopramide: TARDIVE DYSKINESIA (TD) which can be IRREVERSIBLE (D/C if s/sx occur, risk increased w/ renal impairment, longer duration, and total cumulative dose - avoid >12 weeks)

Question 52

Cannabinoids for chemotherapy-induced N/V: -Drugs/Brands -ROA -Adminsitration -AVEs -Warnings

Answer 52

Drugs: dronabinol (Syndros: C-II), marinol (C-III) ROA: PO Administration: -Refrigerate -Dronabinol oral solution contains 50% alcohol AVEs: SOMNOLENCE, EUPHORIA, INCREASED APPETITIE, seizures Warnings: cautionin hx of substance use disorder or psychiatric conditions

Question 53

Chemotherapy Recommendations for: -Pregnancy and Breastfeeding -Chemotherapy handling -Administration and extravasation -Timing of vaccinations

Answer 53

Pregnancy/Breastfeeding: most are highly teratogenic: AVOID CONCEIVING DURING TX, pregnant females should NOT handle chemotherapy drugs Chemotherapy Handling: hazardous drugs, use PPI and USP 800 during compounding Chemotherapy Administration and Extravasation: many are vesicants that can cause tissue necrosis if leaks into vein -DNA-binding (bind to dead and healthy cells): anthracyclines. mitomycin (can use cold compress, dexrazoxane for anthracyclines) -Non-DNA binding (metabolized in tissue and typically less damage): vinca alkaloids (can use warm compress, hyaluronidase can increase absorption and dispersion) -Intrathecal administration: few can be done, must be preservative-free Vaccinations: -Avoid during chemotherapy (antibody response is suboptimal) -do NOT administer live vaccines -If planned chemotherapy, vaccination should precede by >/=2 weeks (live vaccine: >/=4 weeks prior or at least 3 months after D/C of chemotherapy)

Question 54

Cancer Targeted Therapy: Monoclonal Antibodies (MABs) -Define MABs -Why are MABs associated with infusion reactions? Monitoring and management -Nomenclature tips

Answer 54

MABs: large proteins that bind to specific antigens or receptors on the cell surface to cause cell death -Some are conjugated to cyctotoxic drugs or radioactive compounds to help get directly into the cancer cell -Others active the immune system (immunotherapy) Infusion rxns occur because tehy are foreign substances -Usually occurs within first few hours -Monitor: vital signs (BP, HR), s/sx (fever, flushing, dyspnea, rash, anaphylaxis sometimes) -Premedications: premedication with APAP (usually 650mg PO) + diphenhydramine (IV or PO) or another antihistamine -Depending on drug: additional usage of H2RA, steroids, and/or mepreridine for rigors -TX: sympatomatic care (oxygen, brochodilators) Nomenclature: -"tu" = tumor (ex. riTUximab, ceTUximab) -"ci" = circulatory system (ex. bevaCIzumab) -"li" = immune system (ex. ipiLImumab, pembroLIzumab)

Question 55

Rituximab: -Brand -MOA -Safety concerns -Monitoring -Management

Answer 55

Brand: Rituxan MOA: anti-cluster of differentiation (CD) agent --> binds to CD20 antigen expressed on cell surface, causing cell death Safety concerns: hepatitis B reactivation Monitoring: HBV panel prior to TX intiation (surface antigen, core antibody) Management: consider antiviral (etecavir) prophylaxis in select pts

Question 56

Anti-cluster CD of differentiation Agents: what specific CD antigen do the following bind to -Bilnatumomab -Brentuximab vedotin -Daratumumab

Answer 56

Bilnatumomab (Blincyto): CD19 Brentuximab vedotin (Adcetris): CD30 Daratumumab (Darzalex): CD38

Question 57

Cetuximab: -Brand -MOA -Considerations before using -Safety concerns -Monitoring -Management

Answer 57

Brand: Erbitux MOA: epidermal growth factor receptor (EGFR) inhibitor: inhibits pathway involved in cellular proliferation, differentiation, and survival Considerations: -KRAS mutation: perdicts lack of response to anti-EGFR drugs (use if WILD TYPE) -BRAF V600E mutation: must use ONLY IN COMBO w/ BRAF inhibitor Safety concerns: dermatologic toxicity (acneiform rash) Monitoring: acneiform rash usually occurring within 1st two weeks of TX and correlates to response of therapy (rash indicates drug is working) Management: adopt general skin measures (avoid sunlight, use sunscreen and moisturizers), prophylaxis (topical steroids, ABXs)

Question 58

Trastuzumab: -Brand -MOA -Administration -Safety concerns -Monitoring -Management

Answer 58

Brand: Herceptin MOA: human epidermal growth factor receptor 2 (HER2) inhibitor that binds to extracellular ligand domain of HER2 protein to stop signaling pathways and cell proliferation Administration: conventional trastuzumab, ado-trastuzumab emtansine (Kadcyla), and fam-trasuztumab deruxtecan (Enhertu) are NOT interchangable Safety concerns: CARDIOTOXICITY (cardiomyopathy) Monitoring: LVEF using echocardiogram or MUGA scan at baseline and during tx, s/sx of heart failure (SOB, edema)

Question 59

Pertuzumab: -Brand -MOA

Answer 59

Brand: Perjeta MOA: HER2 inhibitor

Question 60

Bevacizumab: -Brand -MOA -Safety concerns -Management

Answer 60

Brand: Avastin MOA: vascular endothelial growth factor (VEGF) inhibitor that inhibits growth of blood vessels needed for tumor proliferation -NO pharmacogenomic testing needed to use agent Safety concerns: -Impaired wound healing (due to decreased blood flow) -Thromboembolic vents (VTE) -Hemorrhage/fatal bleeding -GI perforation Management: do NOT administer for 28 days BEFORE OR AFTER SURGERY

Question 61

Programmed Death Receptor-1 (PD-1) Inhibitors: -Drugs/Brands -MOA -Safety concerns -Management

Answer 61

Drugs: pembrolizumab (Keytruda), nivolumab (Opdivo) MOA: binds to PD-1 receptor on T-cells to block PD-1 ligands from binding, thereby increasing T-cell activation and antitumor response (immunotherapy) Safety concerns: IMMUNE-MEDIATED TOXICITIES (endocrinopthaies, colitis, heptatoxicity, penuomnitis, thyroid disorders) Management: TX of systemic steroids and/or management of specific toxicity

Question 62

Ipilimumab: -Brand -MOA -Safety concerns -Management

Answer 62

Brand: Yervoy MOA: cytotoxic-T-lymphocyte antigen-4 (CTGLA-4) which removes the "brake" from T-cell activation, increasing T-cell responsiveness and antitumor response (immunotherapy) Safety concerns: IMMUNE-MEDIATED TOXICITIES (endocrinopthaies, colitis, heptatoxicity, penuomnitis, thyroid disorders) Management: TX of systemic steroids and/or management of specific toxicity

Question 63

BCR-ABL Inhibitors: -Drugs/Brands -MOA -Safety concerns -Monitoring -Management

Answer 63

Drugs: imatinib (Gleevec), dasatinib (Sprycel), nilotinib (Tasigna) MOA: blocks tyrosine kinase signaling protein produced by BCR-ABL fusion gene (Philadelphia chromosome) that causes uncontrolled cell division Safety concerns: fluid retention, qt prolongation, GI upset Monitoring: s/sx of fluid retention (edema, pleural effusions, ascites), assess QT interval prior to TX initation Management: -Correct preexisting electrolyte abnormalities -Avoid concurrent QT prolonging drugs and strong CYP3A4 inhibitors -Imatinib: must be taken with food or within 1 hour of meal (mimize GI irritation)

Question 64

BRAF Inhibitors: -Drugs/Brands -MOA -Safety concerns

Answer 64

Drugs: dabrafenib (Tafinlar), vemurafenib (Zelboraf) MOA: inhibit certain mutated forms (either BRAF V600E or V600K mutation), blocking tumor cell growth -Require testing prior to use Safety Concerns: -NEW MALIGNANCIES (basal cell carcinoma) -QT PROLONGATION -Febrile rxns, hypersensitivity, skin rash

Question 65

Mitogen-activated extracellular kinase (MEK) 1 and 2 Inhibitors: -Drugs/Brands -MOA -Safety concerns

Answer 65

Drugs: cobimetinib (Cotellic), trametinib (Mekinist) MOA: inhibits MEK, a cell signaling protein drownstream from RAF -Often in combo w/ BRAF inhibitors and assess BRAF status prior to use (MEK is after BRAF in the signaling cascade) Safety concerns: -Retinopathy -Rhabdomyolysis

Question 66

Epidermal Growth Factor Receptor (EGFR) Inhibitors (tyrosine kinase): -Drugs/Brands -MOA -Safety concerns -Management

Answer 66

Drugs: afatinib (Gilotrif), erlotinib (Tarceva) MOA: EGFR gene mutation (exon 19 mutation or exon 21 substitution), inhibitng pathways involved in cellular proliferation, differentiation, and survival Safety concern/Management: dermatologic toxicity (acneiform rash) that usually occurs within 1st two weeks of TX and correlates w/ response to therapy (rash indicates TX is working) -Adopt general skin measures (avoid sunlight, use suncreen and moisturizers) -Prophylaxis (topical steroids or ABXs)

Question 67

Breast Cancer: -Risk factors -Diagnosis -Prophylaxis

Answer 67

Risk factors: female sex (more estrogen and progesterone produced), increasing age, family hx of breast cancer, genetics (BRCA mutation), Klinefelter syndrome (XXY, resulting in more estrogen) Diagnosis: -Breast self-exams: only help indicate need for follow up -Mammogram: identifies abnormal tissue (annual for screening) -Ultrasound: helps differentiate between benign fluid-filled cyst and solid mass -Breast MRI -Biopsy: identifies if cancer cells present (confirmed diagnosis) Prophylaxis: -Surgery (mastectomy) -Premenopausal: SERMs (tamoxifen) -Postmenopausal: selective estrogen modulators aka SERMs (tamoxifen, raloxifene), aromatase inhibitors aka AIs (exemestane, anastrazole)

Question 68

Breast Cancer: TX -General TX if hormone receptor positive (HR+) aka estrogen-receptor positive (ER+) and/or progesterone-receptor positive (PR+) -HER2+ -Triple-negative (ER-, PR-, and HER2-) -Metastatic

Answer 68

HR+ aka Hormone-sensitive: adjuvant hormone therapy for 5-10 years -Premenopausal: females produce estradiol (most potent estrogen): first line is tamoxifen (aromatase inhibitors only prevent conversions to estrogens - MUST be used w/ ovarian ablation/suppression via surgery, radiation, or GnRH agonists) -Postmenopausal: females produce little estradiol: tamoxifen or aromatase inhibitor (AI) HER2+: trastuzumab and other MABs (pertuzumab) Triple-negative: spread faster than other breast cancers and generally worse prognosis: taxane or anthracycline-based chemotherapy preferred Metastatic: often in bone, lungs, liver, and brain; cure may be unlikely -Pallative care -Chemotherapy to srink tumor -Radiation, surgery -Endocrine therapy, HER2+, PIK3CA, PD-L1 biomarker testing/TX

Question 69

Selective Estrogen Receptor Modulators (SERMs): -Drugs/Brands -MOA -AVEs -CIs -BBW -Metabolism

Answer 69

Drugs: tamoxifen (Soltamox), toremifene (Fareston) MOA: binds to estrogen receptors at different sites in the body to block effects (thus can be used in both pre- and post-menopausal women w/ breast cancer) AVEs: HOT FLASHES/NIGHT SWEATS, VAGINAL BLEEDING/DISCHARGE, arthralgia/myalgia, edema, HTN -Tamoxifen: DECREASED BONE MINERAL DENSITIY in premenopausal females and cataracts (supplement w/ vitamin D/Ca++) CI: -Tamoxifen: concurrent use w/ warfarin or hx of DVT/PE, pregnancy (teratogenic: use contraceptives) -Toremifene: QT prolongation, uncorrected hypokalemia/hypomagnesemia BBW: -Tamoxifen: increased RISK OF UTERINE OR ENDOMETRIAL CANCER and thromboembolitic events -Toremifene: QT prolongation Metabolism: tamoxifen is a PRODRUG converted via CYP2D6 -Efficacy decreased from slow metabolizers of CYP2D6 or concurrent use w/ CYP2D6 inhibitors (estrogen, fluoxetine, and paroxetine --> venlafaxine preferred for hot flashes)

Question 70

Fulvestrant: -Brand -MOA -TX -ROA -AVEs

Answer 70

Brand: Faslodex MOA: selective estrogen receptor degrader (SERD) that causes downregulation of estrogen receptors TX: most commonly for ADVANCED breast cancer ROA: IM injection AVEs: INCREASED LFTS, INJECTION SITE PAIN, HOT FLASHES, arthralgia/myalgia, nausea, HA, cough, dyspnea

Question 71

Aromatase Inhibitors (AIs): -Drugs/Brands -MOA -ROA -AVEs -AVEs compared to SERMs

Answer 71

Drugs: anastrozole (Arimidex), letrozole (Femara), exemestane (Aromasin) MOA: blockers peripheral conversion of androgens to estrogen ROA: PO AVEs: HOT FLASHES/NIGHT SWEATS, ARTHRALGIA/MYALGIA, lethargy/fatigue, N/V, rash, hepatotoxicity, HTN, dyslipidemia AVEs compared to SERs: -HIGHER risk of CVD compared to SERMs -HIGHER risk of osteoporosis compared to SERMs (consider Ca/Vitamin D supplementation, weight-bearing exercises, and DEXA screening)

Question 72

Prostate Cancer: -Screening/Diagnosis -Treatment

Answer 72

Screening/Diagnosis: -Prostate specific antigen (PSA): increased with most cancers (>10 ng/mL likely indicates and >4 ng/mL should be investigated) -Digital rectal exam (DREA) and biopsy to confirm cancer TX: -Androgen deprivation therapy (ADT): goal to castrate levels of testosterone with GnRH antagonist or GnRH agonist taken with antiandrogen initially -Metastatic: often castrate-resistant (does NOT respond to ADT) --> second-generation antiandrogen or chemotherapy

Question 73

Gonadrotropin Releasing Hormone (GnRH) Agonists: -Drugs/Brands -MOA -AVEs -CIs

Answer 73

Drugs: leuprolide (Lupron Depot, Eligard, Camcevi), goserelin (Zoladex), histerelin (Supprelin LA), triptorelin (Trelstart) MOA: cause initial surge in testoerone from increased GnRH --> increased LH and FSH levels, but followed by gradual reduction of testosterone though negative feedback loop on hypothalamus ROA: injections -IM: leuprolide, triptorelin -SQ: ALL but triptorellin AVEs: HOT FLASHES, IMPOTENCE, GYNECOMASTIA, BONE PAIN, QT PROLONGATION, injection site pain, dsylipidemia, hyperglycemia -Tumor flare initially: concurrent use w/ antiandrogen (bicalutamide) -Risk of osteoprosis from decreased BMD (Ca/vitamin D supplementation, weight bearing excerises, DEXA scan) CI: pregnancy, breastfeeding

Question 74

Gonadotropin-Releasing Hormone (GnRH) Antagonists: -Drugs/Brand -MOA -ROA -AVEs

Answer 74

Drugs: degarelix (Firmagon), relugolix (Orgovyx) MOA: blocks GnRH receptors, directly causing rapid decrease in testosterone ROA: -SQ injection: degarelix -PO: relugolix AVEs: hot flashes, hypersenstivity rxns, QT prolongation, hyperglycemia -NO tumor flare (antiandrogen NOT needed) unlike GnRH agonists that initially increase testosterone

Question 75

Anti-androgens (First Generation) -Drugs/Brands -MOA -ROA -AVEs -CIs

Answer 75

First gen: bicalutamide (Casodex), flutamide (Eulexin), nilutamide (Nilandron) MOA: competitively inhibit testosterone from binding to prostate cancer cells ROA: PO AVEs: HOT FLASHES, GYNECOMASTIA, hepatotoxicity, increased risk of CVD -Nilutamide: night blindeness and disulfiram rxns (avoid alcohol CI: -Bicalutamide: do NOT use in females -Flutamide, nilutamide: severe hepatic impairment

Question 76

Anti-Androgens (Second Generation): -Drugs/Brands -MOA -ROA -AVEs -Warning

Answer 76

Second gen: apalutamide (Erleada), darolutamide (Nubeqa), enzalutamide (Xtandi) MOA: competitively inhibit testosterone from binding to prostate cancer cells ROA: PO AVEs: HTN, fatigue, increased LFTs, skin rash Warnings: seizures, myocardial ischemia

Question 77

Abiraterone -Brand -MOA -ROA -AVEs -Warnings

Answer 77

Brand: Zytiga, Yonsa MOA: interferes with CYP17 enzyme involved in the synthesis of steroid hormones in the testes and adrenal glands to decrease testosterone production ROA: PO AVEs: edema, HTN, hot flashes, hyperglycemia, increased TGs, hypophosphatemia Warnings: -Hepatotoxicity -Mineralcorticoid excess: fluid retention, increased BP, hypokalemia (reduce excess w/ concurrent prednisone) DDIs: major CYP3A4 substrate (avoid concurrent use w/ inducers or inhibitors)

Question 78

Tumor Lysis Syndrome (TLS): -Define -When does this normally occur -Treatment

Answer 78

TLS: oncologic EMERGENCY where tumors are rapidly broken down and release of their intracellular components (K, Phosphate, Purines, Pyrmidines) can lead to hyperkalemia (arrhythmias), hyperphosphatemia (can precipitate in soft tissues), hypocalcemia from binding of phosphate (anorexia, nausea, seizures), hyperuricemia (damage kidneys) -Severe complications: acute renal failure, cardiac arrest from electrolyte disturbances When: often occurs at initiation of chemotherapy or can occur spontaneously with tumor burden or tumors w/ high proliferative rates (ex. leukemia) TX: -D/C any offending drugs (ex. NSAIDs, thiazides that increase uric acid) for prophylaxis and TX -IV hydration w/ NS (increases urine output and accelerates excretion of excess components) -Electrolyte correction if needed Urate lowering therapies: -Allopurinol prevents nucleic acid conversion to uric acid (for gout usually 100mg QD, but for TLS HIGHER DOSES: 400-800mg/day) and continued until metabolic abnormalities resolved -Alternatively: febuxostat (ex. in pt w/ allopurinol-induced SJS/rash) -Rasburicase when HIGH-risk pts (WBCs >100,000 cells/mm3, Burkitt lymphoma) that may already have high levels of uric acid (>8) since allopurinol which rapidly converts uric acid to more water-soluble metabolite (allantoin) to excrete (CI: G6PD deficiency; D/C STAT and permanently if hemolysis developed)

Question 79

Hypercalcemia of Malignancy: -Why do cancer pts get hypercalcemia? -S/Sx -TX -Drug considerations

Answer 79

Certain cancers can cause calcium to leach from the bones, causing hypercalcemia -Causes: parathyroid hormone-related protein secretion, bone metastases (osteoclast production stimulated), and calcitriol overproduction S/Sx: weak bones/fractures, N/V, fatigue, dehydration/polyuria/polydipsia, confusion/lethargy TX: -Mild (corrected Ca 10.6-<12 mg/dL): hydration -Moderate (corrected Ca 12-13.9) or severe (corrected Ca >14): IV hydration w/ NS + medication to lower Ca (first line: IV bisphosphonate; for refractory: denosumab) -Severe: can add calcitonin on for up to 48 hours (tachyphylaxis can occur quickly thus short duration) Drugs: -IV bisphosphonates = zolderonic acid (Zometa) 4mg once or pamidronate -do NOT confuse zoledronic acid (Reclast) which is dosed as 5mg annually for osteoporosis -Calcitonin: nasal spray NOT effective for hypercalcemia (use IM or SQ); fast onset of 2 hours -Denosumab (Xyega): 120mg SQ Qweekly for up to 3 doses then monthly for persistent hypercalcemia (do NOT confuse w/ Prolia that is dosed 60mg Q6 months for osteoporosis)