62. Oncology II: Common Cancer Types and Treatment Flashcards
Complementary therapy such as __ or ____ is commonly used among cancer patients to manage treatment side effects
Acupuncture
Medical marijuana
What does partial response to treatment mean?
At least 30% of tumor was eliminated
What is the primary treatment if the cancer is resectable?
Surgery to remove the bulk of the tumor
What is the difference between Neoadjuvant therapy vs adjuvant therapy
Neoadjuvant = before surgery to shrink tumor
Adjuvant = after surgery to eradicate residual disease
____ causes ~80% of lung cancers
Smoking
T/F: Use of immunosuppressants post-transplant can increase risk of lung cancer
False - can increase risk of skin cancer
What is the “ABCDE” mnemonic for skin cancer
Asymmetry
Border - edges are irregular, notched
Color - not the same all over
Diameter - larger than 6 mm or the size of the tip of a pencil eraser
Evolving - changing in size, color, shape, or symptoms (itching, bleeding, tenderness)
The biggest risk factor for developing breast cancer is ___
female gender
Rationale: many breast cancer tumors have estrogen receptors that require estrogen to grow (females have more estrogen than males)
What are modifiable risk factors for breast cancer?
Overweight (in post menopausal females)
Low physical activity
Poor nutrition
Tobacco
Alcohol use
____ use low-dose x-rays to identify abnormal breast tissue
Mammograms
___ and ___ genes normally suppress tumor growth. Inherited mutations in either gene prevents cell repair and causes a dramatic increase in breast cancer incidence.
BRCA1
BRCA2
T/F: Less than 5% of breast cancer occurs in males
False - less than 1%
____ is a congenital condition in which males have 1 Y chromosome and 2 or more X chromosomes. Males with this condition produce more estrogen (higher breast cancer risk)
Klinefelter syndrome
If a breast tumor expresses either estrogen or progesterone receptors, the tumor is referred to ____ and classified as ____
Hormone-sensitive
estrogen receptor positive (ER+), progesterone receptor positive (PR+), or both (ER+/PR+)
Hormone-sensitive breast cancers will be treated with adjuvant hormone (endocrine) therapy for ____ years to suppress cancer recurrence. Choice of treatment depends on ____
5-10 years
Menopausal status of the patient
First-line adjuvant treatment for premenopausal females with hormone-sensitive breast cancer is ____
tamoxifen
MOA tamoxifen for breast cancer
Selective estrogen receptor modulator (SERM) and antagonist in breast cells
Why are aromatase inhibitors (AIs) not useful as monotherapy in premenopausal women with breast cancer?
Premenopausal females produce estradiol (most potent estrogen) while postmenopausal females produce very little estradiol and get most of their estrogen from the peripheral conversion of androgens
AIs do not block ovarian estradiol production
MOA aromatase inhibitors for breast cancer
Reduce estrogen production by blocking the aromatase enzyme that catalyzes this conversion
___ is a selective estrogen receptor modulator (SERM) used for breast cancer prevention, not treatment. It is used in (premenopausal/postmenopausal) females at risk for breast cancer.
Raloxifene
Postmenopausal
Raloxifene increases bone density and is also indicated for osteoporosis prevention and treatment. Why is not first-line?
Causes hot flashes and has a risk of blood clots
Aromatase inhibitors (AIs) are typically not useful as monotherapy in premenopausal women. When would AI treatment be a reasonable option in premenopausal women?
Menopause was induced (i.e. ovarian suppression or ablation) by taking a gonadotropin-releasing hormone (GnRH) agonist (goserelin or leuprolide)
GnRH agonist treatment decreases LH and FSH which suppresses ovarian estradiol production
Compare first-line adjuvant treatment between premenopausal females vs postmenopausal females with hormone sensitive breast cancer
Premenopausal: tamoxifen (can use AIs if ovarian suppression or ablation)
Postmenopausal: AIs (second line is tamoxifen)
The ___ oncogene promotes breast tumor growth
HER2/neu (typically referred to as HER2)
T/F: approx 20% of breast tumors overexpress HER2 on the cell surface, which makes the tumor grow quickly
True
What is a common HER2 inhibitor used for HER2 overexpression breast cancer?
Trastuzumab (Herceptin)
How do HER2 proteins on the cell surface accelerate breast tumor growth?
They are coupled (dimerized) to send signals that accelerate cell division and tumor growth
Tamoxifen (Soltamox) is a prodrug converted via ___
CYP2D6
Selective estrogen receptor modulators (SERMs) cause hot flashes/night sweats.
Estrogen (the usual treatment) and fluoxetine and paroxetine (CYP2D6 inhibitors) cannot be used to treat these symptoms. ___ is preferred.
Venlafaxine
Boxed warnings for selective estrogen receptor modulators (SERMs)
Increased risk of uterine or endometrial cancer (tamoxifen)
Increased risk of thromboembolic events (tamoxifen, raloxifene)
Side effects for selective estrogen receptor modulators (SERMs)
Hot flashes/night sweats, vaginal bleeding/spotting, vaginal discharge/dryness/pruritus, decreased libido
Tamoxifen: decreased bone density (premenopausal females) - supplement calcium/vitD, teratogenic - contraception needed premenopausal
Others: edema, weight gain, HTN, mood changes, amenorrhea, arthralgia/myalgia, cataracts (tamoxifen)
Note: raloxifene is also unsafe in pregnancy but only used in postmenopausal females
Example of selective estrogen receptor degrader (SERD)
Fulvestrant (Faslodex) - IM injection
Side effects of fulvestrant (Faslodex)
Increased LFTs, injection site pain, hot flashes
Others: arthralgia/myalgia, nausea, HA, cough, dyspnea
Examples of Aromatase inhibitors (AIs)
Anastrozole (Arimidex)
Others: Letrozole (Femara), Exemestane (Aromasin)
Concerns with aromatase inhibitors
Higher risk of osteoporosis (d/t decreased BMD, consider Ca/VitD supps)
Higher risk of CVD compared to SERMs
Side effects of AIs
Hot flashes/night sweats, arthralgia/myalgia
Others: lethargy/fatigue, N/V, rash, hepatotoxicity, HTN, dyslipidemia
___ cancer is the most common cancer in males in the US
Prostate cancer (lung cancer is the most common in the world)
Prostate-specific antigen (PSA), produced in the prostate gland by normal and cancerous cells,(decreases/increases) with most prostate cancers
Increases
The hormonal treatment for prostate cancer is called ___ or sometimes ___
androgen deprivation therapy (ADT) or sometimes chemical castration
Adverse effects of androgen deprivation therapy (ADT) in prostate cancer
impotence, weakness, hot flashes, and loss of bone density
Androgen deprivation therapy (ADT) in prostate cancer is achieved with either ___ or ___
GnRH antagonist (alone)
GnRH agonist (initially taken with an antiandrogen)
Why are GnRH agonists given with antiandrogens for prostate cancer?
GnRH agonists initially increase release of FSH and LH which increase T, causes tumor flare
Antiandrogens are used initially to prevent tumor flare (decreased T), can be d/c once feedback inhibition suppresses FSH and LH later on
Note: GnRH antagonists do not cause tumor flare, decrease T right away
Examples of GnRH agonists used in prostate cancer
Leuprolide (Lupron Depot)
Goserelin (Zoladex)
Others: histrelin (Supprelin LA), triptorelin (Trelstar)
Concerns with GnRH agonists used in prostate cancer
Decreased bone density, supplement with calcium/VitD
Tumor flare - prevent with concurrent use of an antiandrogen
Side effects of GnRH agonists used in prostate cancer
Hot flashes, impotence, gynecomastia, bone pain, QT prolongation
Others: injection site pain, osteoporosis, shrunken testicles, anxiety, peripheral edema, dyslipidemia, hyperglycemia, loss of muscle mass
Concerns with GnRH antagonists used in prostate cancer
Osteoporosis risk, consider calcium/vitD supplementation
No tumor flare - antiandrogen NOT needed
Examples of GnRH antagonists used in prostate cancer
Degarelix (Firmagon), Relugolix (Orgovyx)
Examples of first-gen antiandorgens used in prostate cancer (with GnRH agonist)
Bicalutamide (Casodex), Flutamide, Nilutamide (Nilandron)
Examples of second-gen antiandrogens used in prostate cancer (with GnRH agonist)
Apalutamide (Erleada), darolutamide (Nubeqa), Enzalutamide (Xtandi)
Side effects of first-gen antiandrogens
Hot flashes, gynecomastia
Others: edema, asthenia, hepatotoxicity, increased risk of CVD, N/V/D
Warnings of second-gen antiandrogens
QT prolongation (apalutamide (Erleada))
Chemotherapy regimens are usually administered in ___ week cycles. The break in treatment allows the patient time to recover from the adverse effects, including ___
2-6 week cycles
Myelosuppression
Cells in the body that are also rapidly dividing, including cells in the ____ are susceptible to the damaging effects of cytotoxic drugs
GI tract, hair follicles, and bone marrow
Body surface area (BSA) Mosteller equation
Sq rt ( [ht (cm) * wt (kg) ]/ 3600)
Chemotherapy drugs that work at G1-phase
Asparaginase, interferons, steroids
G1 = growth phase
Chemotherapy drugs that work at S-phase
Antimetabolites: methotrexate, pemetrexed (folate antimetabolites), fluorouracil (5-FU), Capecitabine
Topoisomerase I inhibitors: irinotecan, topotecan
Remember: AT the S-phase, the DNA replicATes
Chemotherapy drugs that work at G2-phase
Topoisomerase II inhibitors (block DNA coiling and uncoiling, causing DNA to break): Etoposide, bleomycin
G2 = growth phase
Chemotherapy drugs that work at M-phase
Taxanes: palitaxel, docetaxxel
Vinca alkaloids: vincristine, vinblastine
M-phase = mitosis, cell divides into 2 daughter cells
Chemotherapy drugs that are cell-cycle independent
Alkylating agents: cyclophosphamide, ifosfamide
Anthracyclines: doxorubicin, mitoxantrone
Platinum compounds: cisplatin, carboplatin
Remembers: All Awesome Pharmacists
Examples of Alkylating agents used as chemotherapy
Cyclophosphamide, ifosfamide (Ifex)
Carmustin (BiCNU, Gliadel Wafer)
Busulfan (Myleran)
Concerns with cyclophosphamide, ifosfamide use
Hemorrhagic cystitis, ensure hydration and use Mensa (Mesnex)
Mesna = chemoprotectant that must be given ppx with ifosfamide and with high doses of cyclophosmaide
Concerns with busulfan use
Pulmonary toxicity
Examples of platinum-based compounds used as chemotherapy
Cisplatin, carboplatin, oxaliplatin
___ is a/w with the highest incidence of nephrotoxicty and CINV
Cisplatin
Concerns with cisplatin use
Nephrotoxicity, ototoxicity (doses > 100mg/m2/cycle must be confirmed with prescriber
Amifostine (Ethyol) is chemoprotectant given ppx to prevent nephrotoxicity
Highly emetogenic
Boxed warnings platinum-based compounds used as chemotherapy
Anaphylactic-like reactions - risk increases with repeated exposure
Concerns with oxaliplatin use
Acute sensory neuropathy, can be exacerbated by exposure to the cold
QT prolongation
Carbolatin dose Calvert Formula
Total carboplatin dose (mg) = (Target AUC) * (GFR + 25)
GFR is commonly “capped” at 125, CrCl may be used to estimate GFR if not available
All anthrocyclines are a/w with ___ and risk is related to total lifetime cumulative dose the pt receives
Cardiotoxicity (cardiomyopathy and HF)
___ is a chemoprotectant indicated for prevention of doxorubicin induced cardiotoxicity
Dexrazoxane (also used as antidote for accidental doxorubicin extravasation)
Lifetime max cumulative doxorubicin dose
450-550 mg/m2
What is the concern with use of doxorubicin and discoloration of bodily fluids?
Drug is red, causes red discoloration of urine, tears, sweat, and saliva
Boxed warnings for doxorubicin
CV toxicity, vesicant, myelosuppression, secondary malignancy
Side effects for doxorubicin
N/V give antiemetics
What is the concern with use of mitoxantrone and discoloration of bodily fluids?
Drug is blue, causes blue discoloration of urine, sclera and other body fluids
Which anthracycline causes red discoloration vs blue discoloration of bodily fluids?
red = doxorubicin
blue = mitoxantrone
Concerns with use of irinotecan (Camptosar)
Acute cholinergic symptoms (flushing, sweating, abdominal cramps, diarrhea (prevent and/or treat with atropine)
Delayed diarrhea (treat with loperamide)
Boxed warning for diarrhea (early and late)
Etoposide capsule storage notes
Refrigerate capsules
Etoposide IV: PO ratio
1:2 (50% bioavailability)
Concerns with use of etoposide IV
Infusion rate-related hypotension (infuse over at least 30-60 mins)
IV preparation (conc ≤0.4 mg/mL to avoid precipitation) – etoposide phosphate (Etopophos) is water-soluble prodrug, can be higher conc
Use non-PVC IV bag and tubing d/t leaching of DEHP
Boxed warning for bleomycin
Pulmonary fibrosis, anaphylaxis
Concerns with use of Bleomycin
Test dose needed d/t risk of anaphylactoid reactions
Premedicate with APAP to reduce incidence of fever/chills
Max lifetime dose = 400 units d/t pulmonary toxicity risk
Note: NOT myelosuppresive
Side effects of bleomycin
hypersensitivity reaction
Others: pulmonary reactions (including pneumonitis, which may progress to pulmonary fibrosis), mucositis, hyperpigementation, fever, chills, N/V (mild)
Which vinca alkaloids are a/w more CNS toxicity? Bone marrow suppression (myelosuppression)?
CNS toxicity = VinCristine (C!)
Bone marrow suppression = VinBlastine, vinorelBine (B!)
Vinca alkaloids are potent vesicants. What do you do if extravasation occurs?
Warm compress + hyaluronidase
What is the concern with vinca alkaloids and intrathecal administration?
Will cause progressive paralysis and death
IV ONLY
To prevent inadvertent intrathecal administration, how should vincristine be prepared?
In a small IV bag (a piggyback) rather than a syringe
Vincristine is often “capped” at ____ per dose regardless of calculated dose based on body surface area. (higher doses = more neuropathy)
2mg/dose
Side effects of vinca alkaloids
Peripheral sensory neuropathy (paresthesias)
Autonomic neuropathy (gastroparesis, constipation)
SIADH
Boxed warnings for Taxanes
Severe hypersensitivity reactions (Except Abraxane) - d/t solvent systems not the taxane
Myelosuppression
fluid retention (docetaxel)
Which taxanes do not need premedication?
Abraxane (paclitaxel bound to albumin w/o solvent system)
Taxane preparation notes
Use non-PVC bag and tubing (Except Abraxane)
Paclitaxel and cabazitaxel: use 0.22 micron filter
What is the oral prodrug of fluorouracil?
Capecitabine (Xeloda)
___ deficiency increases risk of severe toxicity with capecitabine (Xeloda) use
DPD (dihydropyrimidine dehydrogenase)
___ is given with fluorouracil (5-FU) to increase efficacy (helsp 5-FU bind more tightly to its target enzyme, thymidylate synthetase)
Leucovorin
Boxed warning for capecitabine
Sig increase in INR during and up to 1 month after treatment (monitor INR freq)
Side effects of fluorouracil (5-FU), capecitabine (Xeloda)
Hand-foot syndrome, diarrhea, mucositis
Others: cardiotoxicity, photosensitivity, dermatitis
Contraindications for capecitabine
Severe renal impairment CrCl < 30
With high doses of methotrexate, ___ “rescue” must be given
Leucovorin (or levoleucovorin)
____ is the active form of folic acid that is able to bypass the blocked dihydrofolate reductase enzyme caused by methotrexate
Leucovorin
Why is hydration with IV sodium bicarbonate given with methotrexate?
Alkalize the urine
Decrease risk of nephrotoxicity caused by high doses
If methotrexate is given intrathecally, what do you need to consider?
Preservative-free formulations only
Boxed warning for methotrexate
Myelosuppression and aplastic anemia
Renal damage
Hepatotoxicity
GI toxicity
Teratogenicity/fetal death
Others: immunosuppression, tumor lysis syndrome, dermatologic reactions (SJS/TEN), interstitial pneumonitis
Side effects for methotrexate
Nephrotoxicity (dose related)
Hepatotoxicity (more common with chronic use for autoimmune disease)
Nausea
Mucositis
Others: diarrhea, stomatitis, dizziness, sedation, hand-foot syndrome
Methotrexate (Trexall) RA/psoriasis doses are given ___
weekly, not daily
T/F: Cancer doses of methotrexate are much higher than doses used for rheumatoid arthritis (RA) or psoriasis
True
____ antidote that rapidly lowers methotrexate levels for pts with methotrexate-induced AKI and delayed clearance
Glucarpidase (Voraxaze)
Which drugs decrease clearance of methotrexate?
NSAIDs, salicylates, PPIs
Beta-lactams, sulfonamide abx, probenecid
What color is IV methotrexate?
orangish-yellow
Compare levoleucovorin and leucovorin
Levoleucovorin is the levo (L) isomer of leucovorin
Levoleucovorin is dosed at 1/2 the dose of leucovorin
T/F: Regular folate (folic acid) is used for methotrexate for autoimmune disease indications and cancer
False - NOT effective for high-dose methotrexate (cancer doses), only for autoimmune disease
Which brand name of everolimus is for cancer vs transplant?
Afinitor = cancer
Zortress = transplant
Side effects for everolimus (Afinitor)
Mouth ulcers/stomatitis, rash, interstitial lung disease, peripheral edema, dyslipidemia, increased BP, hyperglycemia
Others: myelosuppression, rash, pruritus, hand0food syndrome, stomatitis, fatigue, N/V/D, renal impairment, increased LFTs
Hints for MAbs used in oncology: Bevacizumab, ramucirumab
“ci” = circulatory system
Inhibit growth of blood vessels (used for solid tumors, like colon cancer or non-small cell lung cancer)
Common toxicities
- inhibition of blood vessel growth»_space; HTN»_space; proteinuria
- hemorrhage or thrombosis may occur
- Impaired wound healing (d/t decreased blood flow)
Hints for MAbs used in oncology: Cetuximab, panitumumab
“tu” = tumor
Inhibits growth factor (EGFR) from binding to surface of tumor cell and promoting cell growth (used for solid tumors, like colon cancer)
Common toxicities
- EGFR»_space; epidermis»_space; skin toxicity (acneiform rash)
- development of rash is correlated with response to therapy
Hints for MAbs used in oncology: Trastyuuzumab, pertuzumab
“tu” = tumor
Inhibits growth factor (HER2) from binding to surface of tumor cell and promoting cell growth (used for solid tumors, like breast cancer)
Common toxicities
- cardiotoxicity
Hints for MAbs used in oncology: rituximab, brentuximab
“tu” = tumor
Binds to antigens expressed on specific hematopoietic cells and causes cell deat (used to treat certain hematologic malignancies, such as non-Hodgkin lymphoma, Hodgkin lymphoma, multiple myeloma)
Common toxicities
- CD antigens are expressed on normal as well as malignant hematopoietic cells»_space; suppression of specific hematopoietic cells, bone marrow suppression, increased risk of viral infections
- Brentuximab vedotin is an antibody-drug conjugate (ADC); the antibody binds to the cell, which enables the cytotoxic drug to enter
Hints for MAbs used in oncology: ipilimumab, pembrolizumab
“li” - immune system
Patient’s immune system becomes overactive»_space; potentially life-threatening immune medicated reactions, such as colitis, hepatic toxicity, thyroid dysfunction, and myocarditis can occur; requires steroid treatment
Concerns with Bevacizumab (Avastin) use
Impairs wound healing; do not administer for 28 days before or after surgery
Bevacizumab (Avastin) should not be administered for ___ before or after surgery
28 days
Boxed warnings for Bevacizumab (Avastin)
Severe/fatal bleeding, GI perforation, surgical wound dehiscence (splitting open)
Which cancer med requires testing for HER2 gene expression?
Trastuzumab (Herceptin) - must have HER2 overexpression to use
Monitoring for trastuzumab (Herceptin)
LVEF (using echocardiogram or MUGA scan)
T/F: Ado-trastuzumab emastine, fam-trastuzumab deruxtecan, and trastuzumab are interchangeable
False
Which cancer med requires testing for EGFR gene expression and KRAS mutation?
EGFR + correlates with better response rates in NSCLC
Must be KRAS wild type to use (KRAS mutation predicts poor response to treatment in colorectal cancer)
Side effects of cetuximab
Acneiform rash
Others: serious skin toxicities (SJS/TEN), ocular toxicities, infusion related reactions, N/V/D, Mg and Ca wasting
T/F: Rash with cetuximab (Erbitux) means the drug is not compatible with the patient and needs to be d/c to avoid complications
False - rash usually occurs within first 2 weeks of treatment and indicates better response to drug
Avoid sunlight and use sunscreen (topical emollients, including topical steroids and abx, can be given ppx to reduce skin damage)
When using Rituximab (Rituxan), what do you use to premedicate?
Diphenhydramine, APAP, and steroid
Boxed warnings for rituximab (Rituxan)
Hep B reactivation, progressive multifocal leukoencephalopathy (PML )
Which cancer med requires hep B panel prior to administration?
Rituximab (Rituxan)
Concerns with pembrolizumab (Keytruda), nivolumab (Opdivo)
Immune mediated toxicities may require interruption or permanent d/c of treatment and treatment with steroids
Which cancer med requires Philadelphia chromosome (BCR-ABL) positive to use?
Imatinib (Gleevec) - used in chronic myelogenous leukemia
Side effects for imatinib (Gleevec)
Fluid retention, QT prolongation
Others: Myelosuppression, N/V/D, edema, skin rash, increased LFTs, HF, HBV reactivation
Which cancer med requires BRAF V600E or V600K mutation positive to use?
BRAF inhibitors (Vemurafenib (Zelboraf), Dabrafenib (Tafinlar))
Warnings for BRAF inhibitors (Vemurafenib (Zelboraf), Dabrafenib (Tafinlar))
New malignancies, such as squamous cell carcinoma and basal cell carcinoma
QT prolongation
Serious skin reactions
hepatotoxicity
Which cancer meds require EGFR mutation positive (Exon 19 or 21) to use?
EGFR inhibitors: Afatinib (Gilotrif), Erlotinib (Tarceva) - used in NSCLC
T/F: Rash with Afatinib (Gilotrif), or Erlotinib (Tarceva) means the drug is not compatible with the patient and needs to be d/c to avoid complications
False - rash usually occurs within first 2 weeks of treatment and indicates better response to drug
Avoid sunlight and use sunscreen (topical emollients, including topical steroids and abx, can be given ppx to reduce skin damage)
Warning for anaplastic lymphoma kinase (ALK) inhibitors (Alectinib (Alecensa), Brigatinib (Alunbrig))
QT prolongation
Others: hepatotoxicity, bradycardia, interstitial lung disease, myalgia, and photosensitivity (alectinib)
What are some common toxicities of tyrosine kinase inhibitors (TKIs)?
Hypothyroidism
QT prolongation
Rash (EGFR TKIs cause severe acneiform rash that is correlated with better efficacy, severe skin reactions (SJS/TEN) possible)
HTN, Hand-foot syndrome: TKIs that target vascular endothelial growth factor commonly a/w causing HTN and hand-foot syndrome (likely d/t interference with growth of blood vessels)
Diarrhea
Hepatic metabolism (CYP3A4 substrate), hepatic toxicity
Which cancer oral agents should be taken with food or within 1 hr after meal?
Imatinib (Gleevec), Capecitabine (Xeloda)
Others: Thalidomie (Thalomid), exemestane (Aromasin)
Which cancer oral agents can be taken without regard to food?
Anastrozole (Arimidex), tamoxifen (Soltamox)
Others: dasatinib (Sprycel), sunitinib (Sutent), bicalutamide (Casodex), enalidomide (Revlimid), letrozol (Femara)
Which cancer oral agents are teratogenic and require 2 neg pregnancy tests prior to starting treatment and use 2 forms of birth controls for female patients of reproductive potential?
Thalidomide, pmalidomide, and lenalidomide
