Oncology Flashcards
Cancer causes
- 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) - External Factors
-Lifestyle: tobacco use, excessive alcohol intake, poor diet, low physical exercise
-Environmental exposure: sunlight, chemicals (benzene, formaldehyde), radiation, viruses - Internal Factors - hormones, older age, inherted gentic mutations
Cancer Prevention Methods
- Avoid tobacco
- Limit alcohol intake
- Maintain healthy lifestyle
- Receive certain vaccinations (ex. HPV)
- Low-dose ASA in select pts for colorectal cancer prevention
- Regular check-ups to assess cancer risk, family hx, and individual hx and getting regular cancer screenings
- Skin protection and screening for abnormal spots
Skin Cancer: risk factors, how to protect skin, and how to screen skin
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)
Colorectal Cancer Screening:
-Age
-Types of tests that can be done
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
For each cancer, list the screening recommendations
-Breast
-Cervical
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
For each cancer, list the screening recommendations:
-Lung
-Prostate
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)
What are the warning signs of cancer (CAUTION)?
-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
Define the following cancer terminology:
-Benign
-Malignant
-Carcinoma
-Leukemia
-Lymphoma
-Multiple myeloma
-Sarcoma
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)
Define the following cancer treatment terminology:
-Neoadjuvant therapy
-Adjuvant therapy
-Complete response
-Partial response
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
Cancer Staging: TNM
T: tumor size
N: node status
M: metastatis
Higher the number, more advanced cancer is
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
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
Where are rapdily dividing cancer cells typically located, and why is this important in context of chemotherapy agents?
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
Chemotherapy calculations:
-Mostellar Equation
-Du bois and Du bois Equation
-Calvert Formula
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
Cyclophosphamide:
-Brand
-MOA
-Safety concerns
-Monitoring
-Management
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
Ifosfamide
-Brand
-MOA
-Safety concerns
-Monitoring
-Management
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
Busulfan
-Brand
-MOA
-Safety concerns
-Monitoring
-Management
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
Carmustine:
-Brand
-MOA
-Safety Concerns
-Monitoring
-Management
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
Cisplatin
-Brand
-MOA
-Safety Concerns
-Monitoring
-Management
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)
Compare cisplatin to carboplatin and oxaliplatin
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)
Doxorubicin:
-Brand
-MOA
-Safety Concerns
-Monitoring
-Management
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
Mitoxantrone:
-Brand
-MOA
-TX
-Safety Concerns
-Monitoring
-Management
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
Irinotecan:
-Brand
-MOA
-Safety Concerns
-Monitoring
-Management
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)
Etoposide:
-MOA
-Safety Concerns
-Monitoring
-Management
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
Vincristine, Vinblastine, and Vinorelbine:
-MOA
-Safety Concerns
-Monitoring
-Management
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
Taxanes:
-Drugs/Brands
-MOA
-Safety Concerns
-Monitoring
-Management
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)
Fluorouracil (5-FU):
-MOA
-Safety Concerns
-Monitoring
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)
Flurouracil (5-FU):
1. What is the prodrug of 5-FU?
- What drug is given simultaneously to increase efficacy?
- What is the antidote of 5-FU toxicities?
- Capecitabine (Xeloda)
- 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
Management of Hand-foot syndrome
- Limit/modify daily activities to reduce friction/pressure (ex. loose-fitting shoes, avoiding tools that require squeezing)
- Avoid heat exposure
- Cold compresses to temporarily relieve pain/tenderness
- EMOLLIENTS (ex. ammonium lactate, urea cream, Aquaphor) to retain moisture
- Topical steroids and pain meds to lessen inflammation and pain
- Dose modifications or therapy interruptions for severe cases (ex. 5-FU)
Management of mucositis
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)
Cytarabine:
-MOA
-Safety concerns
-Monitoring
-Management
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)
Methotrexate:
-Brand
-MOA
-Safety Concerns
-Monitoring
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)
Methotrexate: management of nephrotoxocity
- Leucovorin or L-isomer (levoleucovorin) as “rescue” for doses >/=500mg/m2 to reduce toxicities –> can ALSO use in GI toxicites
- Hydration w/ IV sodium bicarbonate to alkalinize the urine (improves methotrexate solubility)
- Avoid interaction meds (NSAIDs, SALICYCLATES; others: beta-lactams, PPIs, sulfonamide ABXs, probenecid)
- Caution in pts w/ third spacing (ascites, pleural effusions) which delay drug clearance
- Antidote: glucarpidase (Voraxaze) which rapidly lowers methotrexate levels by converting it into inactive metbaolites in methotrexate-induced AKI and delayed clearance
Methotrexate: between autoimmune and oncologic diseases
-What is the typical dose?
-What is used in addition to off-set toxicites?
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
Tretinoin
-MOA/TX of what cancer
-Safety concerns
-Monitoring
-Management
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
Arsenic Trioxide
-Brand
-MOA
-Safety Concerns
-Monitoring
-Management
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
Bleomycin
-Brand
-MOA
-Safety concerns
-Monitoring
-Management
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)
Bortezomib and Carfilzomib:
-Brand
-MOA
-Safety concerns
-Monitoring
-Management
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)
Lenalidomide, pomalidomide, and thalidomide:
-Brand
-MOA
-Safety concerns
-Monitoring
-Management
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
Pegaspargase:
-Brand
-MOA
-Safety Concerns
-Monitoring
-Management
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)
Summary of Chemotherapy Toxicities: ChemoMan
-Head
-Ears
-Mouth
-Chest
-Heart
-Urinary tract
-Bone
-Extremeties
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)
Neutropenia from chemotherapy:
-ANC calculation and interpretation
-Prophylaxis
-Febrile neutropenia diagnosis and TX
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
Myleosuppression:
-Define
-What chemotherapy drugs do NOT cause myleosuppression?
-Explain the process of myleosuppression and recovery
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
Granulocyte Colony-Stimulating Factors (G-CSFs):
-Drugs/Brand
-MOA
-ROA
-AVEs
-Monitoring
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
What are administration/dosing considerations of granulocyte colony-stimulating factors (G-CSFs)?
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)
- 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
- 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
Thrombocytopenia due to chemotherapy TX
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)
Anemia from chemotherapy: Management
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
- Hgb <10g/dL and minimum of two additional months of planned chemotherapy
- The lowest dose to maintain levels is given to avoid RBC transfusions
- ESA D/C following completion of chemotherapy
- Pt has iron stores for ESAs to actually work
Chemotherapy-Induced Nausea and Vomiting (CINV):
1. Define the different types: acute, delayed, anticipatory, breakthrough, and refractory
- Who is more at risk for CINV?
- What drugs are more likely ot cause CINV?
- Complications
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
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
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)
Substance P/Neurokinin Recetor Antagonists (NK1 RAs):
-Drugs/Brands
-ROA
-AVEs
-Administration
-CIs
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)
5-HT3 Receptor Antagonists:
-Drugs/Brands
-ROA
-Adminsitration
-AVEs
-Warnings
-CIs
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)
Dopamine Receptor Antagonists for chemotherapy-induced N/V:
-Drugs/Brands
-ROA
-AVEs
-Warnings
-BBW
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)
Cannabinoids for chemotherapy-induced N/V:
-Drugs/Brands
-ROA
-Adminsitration
-AVEs
-Warnings
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
Chemotherapy Recommendations for:
-Pregnancy and Breastfeeding
-Chemotherapy handling
-Administration and extravasation
-Timing of vaccinations
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)
Cancer Targeted Therapy: Monoclonal Antibodies (MABs)
-Define MABs
-Why are MABs associated with infusion reactions? Monitoring and management
-Nomenclature tips
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)
Rituximab:
-Brand
-MOA
-Safety concerns
-Monitoring
-Management
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
Anti-cluster CD of differentiation Agents: what specific CD antigen do the following bind to
-Bilnatumomab
-Brentuximab vedotin
-Daratumumab
Bilnatumomab (Blincyto): CD19
Brentuximab vedotin (Adcetris): CD30
Daratumumab (Darzalex): CD38
Cetuximab:
-Brand
-MOA
-Considerations before using
-Safety concerns
-Monitoring
-Management
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)
Trastuzumab:
-Brand
-MOA
-Administration
-Safety concerns
-Monitoring
-Management
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)
Pertuzumab:
-Brand
-MOA
Brand: Perjeta
MOA: HER2 inhibitor
Bevacizumab:
-Brand
-MOA
-Safety concerns
-Management
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
Programmed Death Receptor-1 (PD-1) Inhibitors:
-Drugs/Brands
-MOA
-Safety concerns
-Management
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
Ipilimumab:
-Brand
-MOA
-Safety concerns
-Management
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
BCR-ABL Inhibitors:
-Drugs/Brands
-MOA
-Safety concerns
-Monitoring
-Management
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)
BRAF Inhibitors:
-Drugs/Brands
-MOA
-Safety concerns
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
Mitogen-activated extracellular kinase (MEK) 1 and 2 Inhibitors:
-Drugs/Brands
-MOA
-Safety concerns
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
Epidermal Growth Factor Receptor (EGFR) Inhibitors (tyrosine kinase):
-Drugs/Brands
-MOA
-Safety concerns
-Management
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)
Breast Cancer:
-Risk factors
-Diagnosis
-Prophylaxis
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)
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
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
Selective Estrogen Receptor Modulators (SERMs):
-Drugs/Brands
-MOA
-AVEs
-CIs
-BBW
-Metabolism
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)
Fulvestrant:
-Brand
-MOA
-TX
-ROA
-AVEs
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
Aromatase Inhibitors (AIs):
-Drugs/Brands
-MOA
-ROA
-AVEs
-AVEs compared to SERMs
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)
Prostate Cancer:
-Screening/Diagnosis
-Treatment
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
Gonadrotropin Releasing Hormone (GnRH) Agonists:
-Drugs/Brands
-MOA
-AVEs
-CIs
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
Gonadotropin-Releasing Hormone (GnRH) Antagonists:
-Drugs/Brand
-MOA
-ROA
-AVEs
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
Anti-androgens (First Generation)
-Drugs/Brands
-MOA
-ROA
-AVEs
-CIs
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
Anti-Androgens (Second Generation):
-Drugs/Brands
-MOA
-ROA
-AVEs
-Warning
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
Abiraterone
-Brand
-MOA
-ROA
-AVEs
-Warnings
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)
Tumor Lysis Syndrome (TLS):
-Define
-When does this normally occur
-Treatment
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)
Hypercalcemia of Malignancy:
-Why do cancer pts get hypercalcemia?
-S/Sx
-TX
-Drug considerations
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)
